AVP
Vasopressin-neurophysin 2-copeptin precursor (AVP-NPII) [Contains: Arg-vasopressin (Arginine-vasopressin); Neurophysin 2 (Neurophysin-II); Copeptin] [ARVP] [VP]
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All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
Keywords
- aging
- circadian rhythm coupling
- post-translational
modifications
- redox
- sleep-wake cycle
- suprachiasmatic nuclei
Maintenance of the volume and osmolality of body fluids is important, and the adaptive responses recruited to protect against osmotic stress are crucial for survival. The objective of this work was to compare the responses that occur in aging male and female rats during water deprivation. For this purpose, groups of male and female Wistar rats aged 3 mo (adults) or 18 mo (old) were submitted to water deprivation (WD) for 48 h. The water and sodium (0.15 M NaCl) intake, plasma concentrations of oxytocin (OT), arginine vasopressin (AVP), corticosterone (CORT), atrial natriuretic peptide (ANP), and angiotensin II (ANG II) were determined in hydrated and water-deprived animals. In response to WD, old male and female rats drank less water and saline than adults, and both adult and old females drank more water and saline than respective males. Dehydrated old animals displayed lower ANG II plasma concentration and CORT response compared with the respective normohydrated rats. Dehydrated adult males had higher plasma ANP and AVP as well as lower CORT concentrations than dehydrated adult females. Moreover, plasma OT and CORT levels of old female rats were higher than those in the dehydrated old male rats. Relative expression of ANG II type 1 receptor mRNA was decreased in the subfornical organ of adult and old male rats as well as adult female rats in response to WD. In conclusion, the study elucidated the effect of sex and age on responses induced by WD, altering the degree of dehydration induced by 48 h of WD.
MeSH Terms
- Age Factors
- Animals
- Arginine Vasopressin
- Behavior, Animal
- Dehydration
- Drinking
- Female
- Male
- Rats, Wistar
- Sex Factors
- Sodium Chloride
- Subfornical Organ
- Water Deprivation
Keywords
- aging
- hormonal response
- sex differences
- sodium appetite
- thirst
A growing literature associates the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) with affiliative and cognitive outcomes. The majority of this work in humans, however, considers these neuropeptides separately. Also, despite evidence that OT and AVP interact with gonadal hormones, still warranted is an examination of sex and age variations in endogenous neuropeptide levels, their interrelations, and their functional relationships with attachment and cognition in humans. This study measured endogenous plasma OT and AVP levels in generally healthy young (18-31 years) and older (63-81 years) men and women to (i) determine levels of and interrelations between OT and AVP; (ii) explore functional relationships with self-reported attachment (attachment anxiety and avoidance) and performance-based cognition (processing speed, verbal memory); and (iii) identify variations in these effects by sex and age. We observed sex- and age-differential patterns of results: Women had higher plasma OT levels than men and older adults had higher plasma AVP levels than young adults. The two neuropeptides were highly negatively intercorrelated across all groups. Functionally, higher AVP levels were associated with greater attachment anxiety and higher OT and lower AVP levels were associated with faster sensorimotor processing speed, with sex and age moderating these effects. This integrated approach identifies variations in endogenous peripheral neuropeptide levels in humans, supporting their sex- and age-specific role as "difference makers" in attachment and cognition.
MeSH Terms
- Adolescent
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Anxiety
- Avoidance Learning
- Cognition
- Cohort Studies
- Female
- Humans
- Male
- Middle Aged
- Object Attachment
- Oxytocin
- Sex Factors
- Vasopressins
- Young Adult
Keywords
- Age
- Attachment anxiety
- Oxytocin
- Processing speed
- Sex
- Vasopressin
Alterations to arginine vasopressin (AVP) secretion, the urinary bladder urothelium (UT) and other components of the bladder, and the water homeostasis biosystem may be relevant to the pathophysiology of nocturia and nocturnal polyuria (NP). AVP is the primary hormone involved in water homeostasis. Disruption to the physiological release of AVP or its target effects may relate to several urinary disturbances. Circadian dysregulation and the effects of aging, for example, the development of oxidative stress and mitochondrial dysfunction, may play a role in nocturia voiding symptoms. The urinary bladder UT not only acts as a highly efficient barrier that is maintained during the filling and voiding of the urinary bladder, but is also capable of sensory and transducer function through a network of functional receptors and ion channels that enable reciprocal communication between UT cells and neighboring elements of the bladder mucosa and wall. Functional components of the UT (eg, claudins and receptors or ion channels) play important roles in AVP-mediated water homeostasis. These components and functions involved in water homeostasis, as well as kidney function, may be affected by the aging process, including age-related mitochondrial dysfunction. The characteristics of NP are discussed and the association between NP and circadian rhythm is examined in light of reports that suggest that nocturia should be considered as a type of circadian dysfunction. Many possible pathologic mechanisms that underlie nocturia and NP have been identified. Future studies may provide further insight into pathophysiology with the hope of identifying new treatment modalities.
MeSH Terms
- Age Factors
- Aging
- Cell Physiological Phenomena
- Circadian Rhythm
- Homeostasis
- Humans
- Nocturia
- Polyuria
- Urinary Bladder
- Urothelium
- Water
Human postmortem studies as well as experimental animal studies indicate profound changes in neuropeptide expression in the suprachiasmatic nucleus (SCN) in several pathological conditions including hypertension. In addition, animal experimental observations show that the SCN peptides, vasopressin (AVP) and vasoactive intestinal peptide (VIP) are essential for adequate rhythmicity. These data prompted us to investigate whether changes in these neuronal populations could be the cause or consequence of hypertension. Changes in blood pressure and levels of neuropeptide expression in the SCN were determined during development of hypertension in spontaneously hypertensive rats (SHR), in 2K1C reno-vascular induced hypertensive animals and their respective controls. During the pre-hypertensive stage (5 weeks of age), the VIP and AVP content was higher and the somatostatin (SOM) content was lower in the SHR SCN. At the onset of hypertension (12 weeks of age), when blood pressure levels had just reached about 140 mmHg, AVP and SOM content in the SCN was not different anymore in SHRs compared to control, but VIP was still higher. After 16 weeks, the AVP content was decreased, but SOM was increased and the overall level of VIP in the SCN was still higher in SHRs compared to controls. None of the aforementioned changes in the SCN was observed after induction of hypertension in the 2K1C model. However, while VIP was increased in the NTS projecting medial region of the SCN in SHR animals only after the establishment of hypertension, VIP was decreased in the same region in the 2K1C induced hypertensive rats. Consequently, the present findings confirm previous studies in human and rat indicating that changes in the SCN are strongly associated with the development of hypertension. In addition, the changes in peptide content in the 2K1C animals indicate that the SCN is also able to respond to increases in blood pressure.
MeSH Terms
- Aging
- Animals
- Blood Pressure
- Circadian Rhythm
- Hypertension
- Male
- Neuropeptides
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Rats, Wistar
- Suprachiasmatic Nucleus
Keywords
- Circadian rhythm
- blood pressure
- nucleus tractus solitarius
- vasoactive intestinal peptide
- vasopressin
Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Dehydration
- Genome
- Male
- Mass Spectrometry
- Methylation
- Neurosecretory Systems
- Osmolar Concentration
- Osmoregulation
- Pituitary Gland, Posterior
- Promoter Regions, Genetic
- Rats, Wistar
- Supraoptic Nucleus
- Transcription, Genetic
- Transcriptome
Keywords
- Aging
- Gene expression
- Methylation
- Peptidomics
- Supraoptic nucleus
- Vasopressin
Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11β-hydroxysteroid-dehydrogenase-type 2 (11β-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11β-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11β-HSD2 activity were presented as appropriate. Plasma copeptin was higher in men [median 5.2, IQR (3.7-7.8) pmol/L] than in women [median 3.0, IQR (2.2-4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11β-HSD2 activity was high [β (95% CI) = 0.32 (0.17-0.46), P < 0.001] or if age was high [β (95% CI) = 0.34 (0.20-0.48), P < 0.001], but not if either 11β-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10-3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74-1.69), P = 0.605), after full adjustment. Our data suggest that age and apparent 11β-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.
MeSH Terms
- 11-beta-Hydroxysteroid Dehydrogenase Type 2
- Adult
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Cross-Sectional Studies
- Diabetes Mellitus, Type 2
- Female
- Glycopeptides
- Humans
- Insulin Resistance
- Male
- Metabolic Syndrome
- Middle Aged
- Young Adult
Keywords
- 11-β hydroxysteroid dehydrogenase type 2 enzyme
- Aging
- Copeptin
- Insulin resistance
- Interaction
Stressors that disrupt homeostasis advance aging. Glucocorticoids regulate multiple processes that determine the aging trajectory. Debate exists regarding life-course circulating glucocorticoid concentrations. Rodent and nonhuman primate studies indicate circulating glucocorticoids fall from early life. We measured fasting morning cortisol in 24 female baboons (6-21 years, human equivalent ~18-70). We also quantified hypothalamic paraventricular nuclear (PVN) arginine vasopressin (AVP), corticotropin-releasing hormone, steroid receptors, and pituitary proopiomelanocortin immunohistochemically in 14 of these females at 6-13 years. We identified significant age-related 1) linear fall in cortisol and PVN AVP from as early as 6 years; 2) increased PVN glucocorticoid and mineralocorticoid receptors; 3) increased PVN 11β-hydroxysteroid dehydrogenase 1 and 2, regulators of local cortisol production, and 4) decreased pituitary proopiomelanocortin. Our data identify increased age-related negative feedback and local PVN cortisol production as potential mechanisms decreasing PVN drive to hypothalamo-pituitary-adrenal axis activity that result in the age-related circulating cortisol fall. Further studies are needed to determine whether the cortisol fall 1) causes aging, 2) protects by slowing aging, or 3) is an epiphenomenon unrelated to aging processes. We conclude that aging processes are best studied by linear life-course analysis beginning early in life.
MeSH Terms
- Age Factors
- Aging
- Animals
- Arginine Vasopressin
- Biomarkers
- Circadian Rhythm
- Corticotropin-Releasing Hormone
- Feedback, Physiological
- Female
- Hydrocortisone
- Hypothalamo-Hypophyseal System
- Papio
- Paraventricular Hypothalamic Nucleus
- Pituitary-Adrenal System
- Pro-Opiomelanocortin
- Receptors, Steroid
Keywords
- HPA axis (hypothalamus-pituitary-adrenal)
- aging
- baboon
- glucocorticoids
- paraventricular nucleus
Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients, especially in those receiving medications that can cause hyponatremia. Furthermore, elderly patients with an unsteady gait and/or confusion should be evaluated for the presence of mild hyponatremia, and if present, treatment should be initiated. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and hyponatremia corrected, if present.
MeSH Terms
- Aging
- Fractures, Bone
- Humans
- Hyponatremia
- Osteoporosis
Keywords
- Arginine vasopressin
- Falls
- Fractures
- Gait disturbances
- Hyponatremia
- Osteoporosis
We present the novel urine collection method used during in-home interviews of a large population representative of older adults in the United States (aged 62-91, the National Social Life, Health and Aging Project). We also present a novel assay method for accurately measuring urinary peptides oxytocin (OT) and vasopressin (AVP), hormones that regulate social behaviors, stress, and kidney function. Respondents in a randomized substudy (N = 1,882) used airtight containers to provide urine specimens that were aliquoted, stored under frozen refrigerant packs and mailed overnight for frozen storage (-80 °C). Assays for OT, AVP, and creatinine, including freeze-thaw cycles, were refined and validated. Weighted values estimated levels in the older U.S. population. Older adults had lower OT, but higher AVP, without the marked gender differences seen in young adults. Mild dehydration, indicated by creatinine, specific gravity, acidity, and AVP, produced concentrated urine that interfered with the OT assay, yielding falsely high values (18% of OT). Creatinine levels (≥ 1.4 mg/ml) identified such specimens that were diluted to solve the problem. In contrast, the standard AVP assay was unaffected (97% interpretable) and urine acidity predicted specimens with low OT concentrations. OT and AVP assays tolerated 2 freeze-thaw cycles, making this protocol useful in a variety of field conditions. These novel protocols yielded interpretable urinary OT and AVP values, with sufficient variation for analyzing their social and physiological associations. The problem of mild dehydration is also likely common in animal field studies, which may also benefit from these collection and assay protocols.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Creatinine
- Dehydration
- Female
- Humans
- Kidney
- Longitudinal Studies
- Male
- Middle Aged
- Oxytocin
- Risk Factors
- Sex Factors
- Social Behavior
- Stress, Psychological
- United States
- Urine Specimen Collection
- Vasopressins
Keywords
- Creatinine
- Dehydration
- Social behavior
- Stress.
- Urinary oxytocin assay
- Vasopressin
Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion, sex, and advanced age affect urine formation and may contribute to nocturia. Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting duct. Changes in AVP concentration have the greatest relative effects on urine volume when AVP levels are low; therefore small changes can have a large effect on renal water excretion. AVP is the major regulator of water excretion by the kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of several studies show that patients with nocturia had no significant variation in plasma AVP, whereas patients without nocturia had significant diurnal variation in plasma AVP. The V2 receptor gene is located on the X chromosome, which has important sex-specific consequences. For example, mutations in the V2 gene can cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes in water metabolism are associated with overall body composition, kidney, and brain. Older people generally experience decreased extracellular fluid and plasma volume, which leads to increased adverse consequences from net body water gain or loss. Renal function declines with age, and the ability to concentrate urine and conserve sodium is reduced in the elderly. Thirst perception is also decreased in the elderly, who, compared with younger people, tend to hypersecrete AVP in response to higher plasma osmolality, possibly resulting in hyponatremia. These aspects of renal physiology should be considered when antidiuretic drugs are prescribed for the treatment of nocturia.
MeSH Terms
- Aging
- Arginine Vasopressin
- Humans
- Kidney
- Nocturia
- Sex Factors
Keywords
- kidney
- nocturia
- renal function
The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) into pituitary portal system; CRH and AVP stimulate adrenocorticotropic hormone (ACTH) release through specific G-protein-coupled membrane receptors on pituitary corticotrophs, CRHR1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response to ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory, and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.
Keywords
- V1b receptors
- aging
- hypothalamic–pituitary–adrenal axis
- stress
- vasopressin
Our hypothesis is that there is 'wear and tear' in the brain, which is the basis of the process of aging, but that stimulation of brain function may slow down brain aging and diminish the risk for neurodegenerative diseases such as Alzheimer's disease (AD), possibly by activating repair mechanisms. Evidence supporting this hypothesis is presented in this review. During normal aging and in AD, cell loss is not as prominent a phenomenon as is often presumed. In fact, unaltered neuronal numbers have been reported in many brain areas in AD, e.g. in the nucleus basalis of Meynert (NBM) where the number of large neurons decreases while that of small neurons increases. Decreased neuronal activity is an essential characteristic of AD, and a substantial decrease of cerebral glucose metabolism may even precede cognitive impairments. Some hypothalamic neurons remain intact and active during the process of aging, others become even hyperactive, which may lead to disorders. Arginine vasopressin (AVP) levels were found to be higher in the elderly than in young subjects. There is an age-related, sex-dependent activation of the AVP neurons in the supraoptic nucleus (SON) and in the paraventricular nucleus (PVN), which may be the basis of analogous changes in the prevalence of hypertension and hyponatraemia in the elderly. No significant functional loss of magnocellular hypothalamic neurosecretory neurons were found in the SON or PVN in AD. The activity of the corticotrophin releasing hormone (CRH) neurons in the hypothalamic PVN is the basis for the activity of the hypothalamo-pituitary-adrenal (HPA) axis, which is activated during aging in a sex-dependent way, and even more activated in AD. The activated HPA axis is a risk for depression. Environmental stimulation increases brain reserve. An increase in time spent on intellectual activities was associated with a significant decrease in probability to get AD, and occupation has even a stronger indication of diminished risk for dementia. A series of observations showed that a dysfunctional clock may underlie the disordered rhythms in AD. Additional bright light improved the rest-activity rhythms, while giving bright light and/or melatonin to AD patients ameliorated the progression of cognitive and noncognitive symptoms. This implies that neurons affected by AD can still be reactivated if the right stimuli are applied. Unknown diffusible factors from the neural stem cells improve the survival of aged and degenerating neurons in postmortem human brain slice cultures. Gene therapy with nerve growth factor aimed at the NBM showed metabolic activation of various brain regions. A microarray study of the prefrontal cortex in the course of AD revealed an increased expression of genes related to synaptic activity and changes in plasticity during the very early pre-symptomatic stages, which is proposed to represent a coping mechanism against increased soluble β-amyloid levels. In brief, these examples of the 'use it or lose it' principle during the course of aging or AD now provide novel targets for the development of therapeutic strategies aiming at the prevention and treatment of AD.
MeSH Terms
- Aging
- Brain
- Dementia
- Female
- Humans
- Hypothalamus
- Male
- Neurons
The available evidence continues to illustrate an inhibitory influence of male gonadal activity on the hypothalamic-pituitary-adrenal (HPA) axis under acute stress. However, far less is known about how these systems interact during repeated stress. Because HPA output consistently declines across studies examining repeated restraint, the potential mechanisms mediating this habituation are often inferred as being equivalent, even though these studies use a spectrum of restraint durations and exposures. To test this generalisation, as well as to emphasise a potential influence of the male gonadal axis on the process of HPA habituation, we compared the effects of two commonly used paradigms of repeated restraint in the rodent: ten daily episodes of 0.5 h of restraint and five daily episodes of 3 h of restraint. Both paradigms produced comparable declines in adrenocorticotrophic hormone and corticosterone between the first and last day of testing. However, marked differences in testosterone levels, as well as corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) expression, occurred between the two stress groups. Plasma testosterone levels remained relatively higher in animals exposed to 0.5 h of restraint compared to 3 h of restraint, whereas forebrain gonadotrophin-releasing hormone (GnRH) cell counts increased in both groups. AVP mRNA was increased after 3 h, but not after 0.5 h of repeated restraint, in the medial parvicellular paraventricular nucleus and in the posterior bed nucleus of the stria terminalis (BST), and increased with 0.5 h of repeated restraint in the medial amygdala. CRH mRNA was increased after 3 h, but not after 0.5 h of repeated restraint, in the central amygdala and anterior BST. The data obtained illustrate that, despite comparable declines in HPA responses, the pathways recruited for stress adaptation appear to be distinct between restraint groups. Given the extreme sensitivity of limbic AVP to testosterone, and conversely CRH to circulating glucocorticoids, whether differences in endocrine profiles might explain these neuropeptide differences remains to be seen. Nonetheless, the present study provides several new entry points for testing gonadal influences on stress-specific HPA habituation.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Brain
- Corticosterone
- Corticotropin-Releasing Hormone
- Habituation, Psychophysiologic
- Hormones
- Hypothalamo-Hypophyseal System
- Male
- Neuropeptides
- Pituitary-Adrenal System
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Restraint, Physical
- Stress, Psychological
- Testis
- Testosterone
- Time Factors
Adaptation to stress is a fundamental component of life and the hypothalamo-pituitary-adrenocortical axis (HPA) plays a crucial role in it. The place of cannabinoid influence seems to be in the brain, especially where corticotropin releasing hormone and vasopressin (AVP) secreting neurons are located. The role of AVP is considered to be more important in young than in adult rats. Here we addressed the question if cannabinoid-mediated regulation of the HPA involves AVP and if there is any difference between young and adult rats in this process. 10-day-old and adult AVP deficient Brattleboro rats were compared with their heterozygous littermates 1h after WIN 55,212-2 (6mg/kg i.p.) injection. In control animals the injection led to elevated adrenocorticotropin (ACTH) and corticosterone hormone levels at both ages without remarkable age difference in ACTH levels while all corticosterone levels of adults was approximately 10-times higher. The ACTH secretion of young AVP deficient rats failed to react to WIN 55,212-2 injection while their corticosterone levels were even higher than their littermates. In contrast in adult the role of AVP was diminished. We can conclude that the peripheral administration of cannabinoids leads to HPA axis stimulation, which process involves AVP at least in the young rats. The discrepancy between ACTH and corticosterone levels in young rats suggests an alternative adrenal gland regulatory pathway, which might be present in all studied animals. However, it comes to the front just in AVP deficient pups.
MeSH Terms
- Adrenal Glands
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Benzoxazines
- Cannabinoids
- Corticosterone
- Hypothalamus
- Male
- Morpholines
- Naphthalenes
- Pituitary Gland
- Rats
- Rats, Brattleboro
- Rats, Wistar
The study was undertaken to determine whether ageing affects kidney expression of the aquaporin-2 (AQP2) water channel in glucocorticoid-deficient rats. After adrenalectomy, 6- and 52-week-old Sprague-Dawley rats received aldosterone via osmotic minipumps (glucocorticoid-deficient rats). Aldosterone and dexamethasone were administered to control rats of the same age. An acute water load test verified impairment of water excretion in both young and aged rats with glucocorticoid deficiency, with a more serious impairment in the older rats. Despite the presence of hypoosmolality, non-suppressible release of arginine vasopressin (AVP) was particularly evident in the aged rats with glucocorticoid deficiency in comparison with the young rats. The expression levels of AQP2 mRNA and protein were lower in the aged rats, with a particularly large reduction in AQP2 protein expression. AQP2 expression levels were significantly augmented in the glucocorticoid-deficient rats compared with the controls under both basal and water-loaded conditions. Acute water loading did not suppress expression of AQP2 mRNA and protein, and the percentage increases in AQP2 mRNA and protein expression vs. the respective controls were more pronounced in the 52-week-old glucocorticoid-deficient rats compared with the 6-week-old rats. The findings indicate that upregulation of AQP2 expression is maintained dependent upon non-suppressible release of AVP in rats with glucocorticoid deficiency, and that AQP2 plays a crucial role in persistent impairment of water excretion in aged rats with glucocorticoid deficiency.
MeSH Terms
- Adrenalectomy
- Aging
- Aldosterone
- Animals
- Aquaporin 2
- Arginine Vasopressin
- Dexamethasone
- Epithelial Sodium Channels
- Glucocorticoids
- Kidney
- Male
- Osmolar Concentration
- Rats
- Rats, Sprague-Dawley
- Sodium
- Up-Regulation
- Urine
- Vasopressins
- Water
Arginine vasopressin (AVP) has received increased attention in equine critical care but there is minimal information of AVP concentration in foals. The clinical usefulness of measuring AVP in ill foals depends on knowledge of age-related changes in AVP concentrations in healthy foals. Plasma AVP concentrations will be significantly different when measured from birth to 3 months of age in healthy foals. Thirteen healthy university-owned foals. Prospective, observational study. Blood was collected from healthy foals at birth and 3, 5, 7, 10, 14, 21, 28, 42, 56, and 84 days of age. Plasma was harvested and plasma AVP concentrations were determined by radioimmunoassay. No statistically significant differences were detected in plasma AVP concentrations over the study period. Plasma AVP concentrations over the entire study period was 6.2 /-2.5 pg/mL. There was no age-related variation in plasma AVP concentrations detected in healthy foals from birth to 3 months of age suggesting that AVP concentrations are similar across foals of these ages.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Female
- Horses
- Male
- Vasopressins
Arginine vasopressin (AVP) is an important regulator of cardiovascular homeostasis in the fetus, but its role after birth is unclear. Although infused AVP increases mean arterial pressure (MAP) during the 1st mo after birth, pressor responses are unchanged, suggesting that vascular responsiveness is also unchanged. Alternatively, this could reflect increases in AVP metabolic clearance rate (MCR(AVP)). However, newborn AVP metabolism and synthesis are poorly studied. Therefore, we examined the pressor responses to infused AVP and the pattern of circulating AVP, AVP production rate (PR(AVP)), and MCR(AVP) in conscious newborn sheep (n = 5) at 9-38 days after birth. Basal MAP rose and heart rate (HR) fell during the study period (P < or = 0.02), while circulating AVP was unchanged (P > 0.1), averaging 3.01 /- 0.86 pg/ml. Infused AVP elicited steady-state responses at 10-40 min, increasing plasma AVP and MAP and decreasing HR (P < 0.001). Although pressor responses were unchanged between 9 and 38 days, the rise in MAP correlated with increases in plasma AVP (R = 0.47, P = 0.02, n = 24). MCR(AVP) was unchanged throughout the 1st mo (P > 0.2), averaging 205 /- 17 ml.kg(-1).min(-1), and was associated with an elevated PR(AVP), 973 /- 267 pg.kg(-1).min(-1), which also was unchanged (P > 0.1). After birth, MCR(AVP) and PR(AVP) are elevated, probably accounting for the stable plasma AVP levels. The former is also likely to account for the stable pressor responses to infused AVP during the 1st mo. The reason for the elevated PR(AVP) is unclear but may relate to increases in vascular volume associated with postnatal growth.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Blood Pressure
- Growth
- Heart Rate
- Homeostasis
- Metabolic Clearance Rate
- Sheep
Normal aging is associated with water homeostasis impairment, arginin-vasopressin (AVP) neuron dysfunction and cerebral insulin growth factor-I (IGF-I) expression deficit. Therefore, we aimed at investigating whether a cerebral chronic treatment of IGF-I in aged rats (26-mo) could restore diuretic function comparable with that observed in adults (3-mo). By using osmotic pumps, we have shown that in aged rats, IGF-I treatment in the third ventricle for four weeks increases water intake and restores diuresis and AVP plasma release similar with that observed in adults. The decrease in AVP plasma release induced by brain IGF-I treatment was also associated with the decrease in urinary osmolality. These results indicate that the age-dependent IGF-I deficit in the brain may be involved in the age-impaired fluid homeostasis in rats.
MeSH Terms
- Aging
- Analysis of Variance
- Animals
- Arginine Vasopressin
- Brain
- Catheterization
- Diuresis
- Drinking Behavior
- Homeostasis
- Insulin-Like Growth Factor I
- Male
- Osmolar Concentration
- Rats
- Rats, Wistar
- Urine
- Water
The precise mechanisms regulating gene expression of thrombospondins (TSPs) in the heart remain incompletely understood. Here we characterized cardiac TSP-4 expression in response to pressure overload and myocardial infarction in vivo. Arginine(8)-vasopressin (AVP) infusion increased left ventricular (LV) TSP-4 mRNA levels within 30 min. Also angiotensin II infusion rapidly activated LV TSP-4 expression, TSP-4 mRNA levels being highest at 6h and protein at 72 h and 2 weeks. During remodeling process following myocardial infarction, LV TSP-4 mRNA levels increased at day one, as studied by quantitative RT-PCR. TSP-4 immunostaining was localized to endothelial cells in hypertrophied hearts of spontaneously hypertensive rats. AVP-infusion increased LV TSP-1 mRNA levels similarly to TSP-4 within 30 min showing that rapid induction of gene expression, well before the development of cardiac hypertrophy, is typical for the thrombospondin family. These results further suggest that TSP-4 may be an endothelial specific marker of cardiac overload.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Heart
- Male
- Myocardial Infarction
- Pressure
- Rats
- Rats, Inbred Strains
- Thrombospondin 1
- Thrombospondins
- Transcriptional Activation
- Up-Regulation
- Ventricular Remodeling
Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin (AVP)/V(2) receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 (AQP2) water channel in the inner medullary collecting duct (IMCD). We showed previously that dDAVP administration could partially correct this defect. Since AQP2 can also be regulated by AVP-independent pathways in water deprivation (WD), we investigated AQP2 and phosphorylated AQP2 (p-AQP2) regulation in thirsted adult (10 mo old) and senescent (30 mo old) female WAG/Rij rats. Following 2-day WD, urine flow rate decreased and urine osmolality increased in both groups. However, in agreement with significantly lower cortico-papillary osmotic gradient with aging, urine osmolality remained lower in senescent animals. WD induced sixfold increase of plasma AVP in all animals which, interestingly, did not result in higher papillary cAMP level. Following WD, AQP2 and p-AQP2 expression increased hugely in 10- and 30-mo-old rats and their mistargeting in old animals was corrected. Moreover, the age-related difference in AQP2 regulation was abolished after WD. To further investigate the mechanism of AQP2 underexpression with aging, AQP2 mRNA was quantified by real-time RT-PCR. In the outer medulla, preservation of AQP2 protein expression was achieved through increased AQP2 mRNA level in senescent rats. In the IMCD, no change in AQP2 mRNA was detected with aging but AQP2 protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of AQP2 with aging, which is abolished by WD.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Cyclic AMP
- Cyclic GMP
- Down-Regulation
- Female
- Kidney Concentrating Ability
- Kidney Medulla
- Osmolar Concentration
- Phosphorylation
- RNA Processing, Post-Transcriptional
- RNA, Messenger
- Rats
- Rats, Inbred Strains
- Reverse Transcriptase Polymerase Chain Reaction
- Water Deprivation
- Water-Electrolyte Balance
Neonatal foals succumb rapidly to hypovolaemic shock in comparison to mature horses; they do not consistently increase their heart rate in response to hypotension and respond differently to fluid administration. The hormonal responses to hypovolaemia in the horse and foal require investigation. The hormonal responses to hypovolaemia and fluid administration differ between mature and neonatal horses. Five mature horses and 5 neonatal foals fulfilling predetermined criteria for hypovolaemia, were included in the study. A blood sample was taken at admission and after normalisation of fluid balance. These were analysed for plasma aldosterone, vasopressin (AVP) and atrial natriuretic peptide (ANP). Normally distributed variables were compared using the Student's t test and nonparametric data using the Mann-Whitney U test. ANP, AVP and aldosterone were higher before fluid resuscitation than after fluid resuscitation in mature horses. Aldosterone was higher before than after fluid resuscitation in foals, and was higher in foals both before and after fluid resuscitation than in mature horses. ANP was lower in mature horses after fluid resuscitation than in foals. No other comparisons were significantly different. The hormonal responses of the mature and neonatal horses are different during hypovolaemia and following fluid resuscitation. The differences in the hormonal responses to hypovolaemia and fluid resuscitation may be important when considering fluid resuscitation of hypovolaemic horses and foals, and warrants further investigation.
MeSH Terms
- Aging
- Aldosterone
- Animals
- Animals, Newborn
- Atrial Natriuretic Factor
- Body Fluids
- Female
- Fluid Therapy
- Horse Diseases
- Horses
- Hypovolemia
- Male
- Statistics, Nonparametric
- Treatment Outcome
- Vasopressins
In hamsters (Mesocricetus auratus), anabolic-androgenic steroid (AAS) exposure during adolescence facilitates offensive aggression that is correlated with the enhanced development of the arginine vasopressin (AVP) neural system and reduced development of the serotonin (5-HT) neural system in the anterior hypothalamus (AH). This study examined the temporal onset of these effects by measuring aggression and AH AVP and 5-HT during progressively shorter periods of AAS exposure during adolescent development. The authors tested adolescent hamsters that received AAS for 3, 7, 14, or 28 days for offensive aggression and then examined the hamsters for AVP/5-HT afferent innervation to the AH using immunohistochemistry. While reductions in AH 5-HT afferent innervation were detectable by 7 days of AAS exposure, no concomitant increases in offensive aggression were observed compared to oil-treated littermates. In contrast, by Day 14 of AAS treatment, AH AVP and offensive aggression were significantly higher than oil-treated controls. These data indicate that relatively short-term adolescent AAS exposure alters aggression and AH 5-HT and AVP development, yet only alterations in AH AVP development correlate with temporal onset of the aggressive behavioral phenotype during adolescent AAS exposure.
MeSH Terms
- Aggression
- Aging
- Anabolic Agents
- Androgens
- Animals
- Cricetinae
- Hypothalamus, Anterior
- Image Processing, Computer-Assisted
- Immunohistochemistry
- Male
- Mesocricetus
- Serotonin
- Steroids
- Vasopressins
The aim of the present study is to compare c-fos expression in identified hypothalamic vasopressin (AVP) and oxytocin (OT) neurons in developing (PN7 and PN14) and adult rats following hypophysectomy using dual-labeled immunostaining. Our results showed that hypophysectomy induced c-fos expression in supraoptic (SON) and paraventricular (PVN) nuclei in both the developing and adult rats. Few or no positive cells were observed in the same nuclei in sham-operated animals. Quantitative analysis for c-fos and either of the above named neuropeptides revealed that almost all AVP and OT neurons in the adult and PN14 groups expressed c-fos in response to hypophysectomy. In PN7, hypophysectomy also induced all AVP neurons to express c-fos in SON and PVN. However, few OT neurons in the SON and PVN produced c-fos after hypophysectomy. In addition, the time course of c-fos expression was different in the developing and adult rats after hypophysectomy. The c-fos expression in the developing rats exhibited a more prolonged induction in which staining for c-fos persisted for at least 3 days after hypophysectomy compared with that in the adult in which c-fos immunoreactivity disappeared within 24 hr post-lesion. This study demonstrates that c-fos expression after hypophysectomy is regulated differently during development.
MeSH Terms
- Aging
- Animals
- Hypophysectomy
- Immunohistochemistry
- Male
- Microscopy, Confocal
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Proto-Oncogene Proteins c-fos
- Rats
- Rats, Sprague-Dawley
- Supraoptic Nucleus
- Time Factors
- Up-Regulation
- Vasopressins
Since the neurohypophyseal hormone 8-arginine vasopressin (AVP) is involved in cardiovascular tissue hypertrophy and myocyte differentiation, it is possible that local AVP plays a role in heart maturation. AVP-specific RIA, RT-PCR, and immunoblot measurement of AVP receptors (VR) were used to investigate heart tissues from newborn and adult rats. To test AVP's role in differentiation and specialization into ventricle-like cardiomyocytes, we studied GFP-P19Cl6 stem cells, which express green fluorescence protein (GFP) reporter under transcriptional control of the myosin light chain-2v promoter. VR(1) transcripts and proteins were higher in adult than in newborn rat hearts. In contrast, VR(2) increased from postnatal day 1 to 5 and was barely detected in the adult rat heart. In cardiomyocytes expressing troponin C, immunofluorescence revealed VR(2) and VR(1). Intracellular cAMP increased 6.5- and 8.9-fold in response to the selective VR(2) agonist 1-desamino-8-D-AVP (DDAVP) after 1 and 24 h, respectively. Cardiac AVP was high in 1- and 5-day-old (330 /- 26 and 276 /- 53 pg/mg protein, respectively) but low in 66-day-old (98 /- 15 pg/mg protein) rats. AVP immunostaining was detected in the tunica adventitia and endothelium of the coronary vessels. The possible role of AVP in cardiomyogenesis was indicated by DDAVP-AVP-dependent differentiation of GFP-P19Cl6 stem cells into contracting cells displaying GATA-4, a cardiac-specific marker, and ventricle-specific myosin light chain. Together, it is suggested that the AVP system is implicated in postnatal cardiac maturation.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Cell Differentiation
- Cell Line, Tumor
- Cyclic AMP
- Deamino Arginine Vasopressin
- Female
- GATA4 Transcription Factor
- Genes, Reporter
- Green Fluorescent Proteins
- Heart
- Hormone Antagonists
- Male
- Myocardium
- Myocytes, Cardiac
- Myosin Light Chains
- Oxytocin
- Promoter Regions, Genetic
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Receptors, Vasopressin
- Signal Transduction
- Stem Cells
Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (U(osm)) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, U(osm) (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male U(osm). Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Female
- Humans
- Kidney Concentrating Ability
- Kidney Diseases
- Male
- Middle Aged
- Osmolar Concentration
- Sex Characteristics
- Sodium, Dietary
The implementation of experimental gene therapy in animal models of neuroendocrine diseases is an area of growing interest. In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, and in Koletsky (fa(k)/fa(k)) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. In the above models, viral vectors expressing AVP, leptin receptor b and proopiomelanocortin, respectively, were stereotaxically injected in the relevant hypothalamic regions. In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons, which are involved in the tonic inhibitory control of prolactin secretion and lactotropic cell proliferation. Stereotaxic injection of an adenoviral vector expressing insulin-like growth factor I corrected their chronic hyperprolactinemia and restored TIDA neuron numbers. Spontaneous intermediate lobe pituitary tumors in a retinoblastoma (Rb) gene mutant mouse were corrected by injection of an adenoviral vector expressing the human Rb cDNA and experimental prolactinomas in rats were partially reduced by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidine kinase suicide gene. These results suggest that further implementation of gene therapy strategies in neuroendocrine models may be highly rewarding.
MeSH Terms
- Aging
- Animals
- Animals, Genetically Modified
- Endocrine System Diseases
- Genes, Transgenic, Suicide
- Genetic Therapy
- Hypothalamus
- Mice
- Mutant Proteins
- Neurosecretory Systems
- Pituitary Gland
- Pituitary Neoplasms
- Rats
- Rats, Brattleboro
- Receptors, Cell Surface
- Receptors, Leptin
- Retinoblastoma
In humans, activity rhythms become fragmented and attenuated in the elderly. This suggests an alteration of the circadian system per se that could in turn affect the expression of biological rhythms. In primates, very few studies have analyzed the effect of aging on the circadian system. The mouse lemur provides a unique model of aging in non-human primates. To assess the effect of aging on the circadian system of this primate, we recorded the circadian and daily rhythms of locomotor activity of mouse lemurs of various ages. We also examined age-related changes in the daily rhythm of immunoreactivities for vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) in suprachiasmatic nucleus neurons (SCN), two major peptides of the biological clock. Compared to adult animals, aged mouse lemurs showed a significant increase in daytime activity and an advanced activity onset. Moreover, when maintained in constant dim red light, aged animals exhibited a shortening of the free-running period compared to adult animals. In adults, AVP immunoreactivity (ir) peaked during the second part of the day, and VIP ir peaked during the night. In aged mouse lemurs, the peaks of AVP ir and VIP ir were significantly shifted with no change in amplitude. AVP ir was most intense at the beginning of the night; whereas, VIP ir peaked at the beginning of the daytime. A weakened oscillator could account for the rhythmic disorders often observed in the elderly. Changes in the daily rhythms of AVP ir and VIP ir may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby modify the expression of some biological rhythms.
MeSH Terms
- Aging
- Animals
- Arginine
- Behavior, Animal
- Biological Clocks
- Cheirogaleidae
- Circadian Rhythm
- Neuropeptides
- Peptides
- Primates
- Suprachiasmatic Nucleus
- Time Factors
- Vasoactive Intestinal Peptide
- Vasopressins
Many histochemical investigations indicated that the oxytocin (OXY), the arginine vasopressin (AVP) and the nitric oxide synthase (NOS) have been synthesized in the supraoptic nucleus (SON) neurons. The objective of this study was to examine the age-related expression of the OXY, the AVP and the NOS in the SON of the young adult (2-month-old) and the aged (24-month-old) rats. The histochemistry for reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d; marker for the NOS) and the double labeling histochemistry for the OXY/NADPH-d or the AVP/NADPH-d were employed, and the quantitative analysis was performed with a computer-assisted image processing system. In comparison of the young adult and the aged group, the cell number, the cell size and the reactive density of the NOS-expressing neurons showed a significant increase along with age, and these evidences suggested the age-related increase of the nitric oxide (NO) production. The age-related significant increase was not detected in the number of the OXY/NOS-expressing neurons in the dorsal part, but was detected in the number of the AVP/NOS-expressing neurons in the ventral part. Based on our histochemical findings and reports demonstrated by other authors, we attempted to discuss the physiological role of NOS for the secretion of posterior pituitary hormones along with age.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Image Processing, Computer-Assisted
- Immunohistochemistry
- Male
- NADPH Dehydrogenase
- Neurons
- Nitric Oxide Synthase Type I
- Oxytocin
- Rats
- Rats, Sprague-Dawley
- Supraoptic Nucleus
The limited renal concentration performance by the immature kidney traditionally is thought to be attributed to blunted renal response to arginine vasopressin (AVP) and medullary hypotonicity. The diminished AVP-dependent osmotic water permeability of the collecting duct is the result of decreased AVP binding and adenylate cyclase activation, and low expression of aquaporin-2 (AQP2) mRNA and low levels of AQP2 protein. Moreover, the immature kidney fails to establish deep cortico-papillary osmotic gradient because of structural immaturity, limited solute transport and increased medullary blood flow. Based on indirect clinical and experimental evidences this article puts forward a hypothesis that during perinatal period the abundant hyaluronan (HA) content in the renomedullary interstitium has a primary role in antagonizing water reabsorption and limiting concentration performance. Hydration-related alterations in renal HA appears to be mediated by antidiuretic hormone. The concept of HA-mediated renal water transport may imply that interfering selectively with renal HA metabolism may provide a new therapeutic approach to promote diuresis or antidiuresis, respectively, according to the elevation or reduction in renomedullary HA.
MeSH Terms
- Aging
- Animals
- Body Water
- Evidence-Based Medicine
- Humans
- Hyaluronic Acid
- Kidney
- Models, Biological
- Urination
- Water-Electrolyte Balance
The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Cell Count
- Cheirogaleidae
- Circadian Rhythm
- Gene Expression Regulation
- Immunohistochemistry
- Male
- Neurons
- Suprachiasmatic Nucleus
- Vasoactive Intestinal Peptide
Detection and pharmacological characterization of OT-binding sites were performed on 12-day-old rat spinal cord membranes and on embryonic cultured spinal neurones and astrocytes after 12 days in culture. In neurone-enriched cultures, OT-binding sites were detected by autoradiography on cells morphologically comparable to neurone-specific enolase immunoreactive cells. In astrocyte cultures, as shown by combination of autoradiography and immunocytochemistry, OT-binding sites were detected on cells expressing the glial fibrillary acidic protein (a specific astrocytic marker). The pharmacological characterization was assessed by binding studies performed with a highly specific radioiodinated OT antagonist on postnatal rat spinal cord membranes and on embryonic cultured spinal cord neurones and astrocytes. The saturation studies suggested the presence of a single class of binding sites of high affinity for the OT antagonist on spinal membranes and cultured cells, as already described in the rat for central and peripheric OT receptors. The competition studies indicated that on spinal membranes, OT and AVP had the same high affinity, as classically described, whereas on cultured cells, AVP had a lower affinity, suggesting that culture conditions may influence the pharmacology of the spinal OT-binding sites. Involvement of NEM- and Gpp[NH]p-insensitive G-proteins in the coupling of the spinal OT-binding sites with the effector system was evidenced on 12-day-old rat spinal membrane preparations and on neurone and astrocyte cultures.
MeSH Terms
- Aging
- Animals
- Astrocytes
- Binding Sites
- Ethylmaleimide
- Guanylyl Imidodiphosphate
- Magnesium
- Neurons
- Oxytocin
- Rats
- Rats, Wistar
- Spinal Cord
Renal concentrating ability is known to be impaired with aging. The antidiuretic hormone AVP plays an important role in renal water excretion by regulating the membrane insertion and abundance of the water channel aquaporin-2 (AQP2); this effect is primarily mediated via the V2 subtype of the AVP receptor (V2R). This study evaluated the hypothesis that decreased renal sensitivity to AVP, with subsequent altered renal AQP2 expression, contributes to the reduced urinary concentrating ability with aging. Our results show that under baseline conditions, urine osmolality is significantly lower in aged Fischer 344 and Brown-Norway F1 hybrid (F344BN) rats despite equivalent plasma AVP concentrations as in young rats. Levels of kidney V2R mRNA expression and AQP2 abundances were also significantly decreased in aged F344BN rats, as was AQP2 immunostaining in collecting duct cells. In response to moderate water restriction, urine osmolality increased by significantly lesser amounts in aged F344BN rats compared with young rats despite similar increases in plasma AVP levels. Moderate water restriction induced equivalent relative increases in renal AQP2 abundances in all age groups but resulted in significantly lower abundances in total kidney AQP2 protein in aged compared with young F344BN rats. These results therefore demonstrate a functional impairment of renal concentrating ability in aged F344BN rats that is not due to impaired secretion of AVP but rather appears to be related to impaired responsiveness of the kidney to AVP that is secondary, at least in part, to a downregulation of renal V2R expression and AQP2 abundance.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Aquaporins
- Arginine Vasopressin
- Dehydration
- Down-Regulation
- Gene Expression
- Immunohistochemistry
- Kidney
- Kidney Concentrating Ability
- Male
- RNA, Messenger
- Rats
- Rats, Inbred F344
- Receptors, Vasopressin
- Urine
- Water-Electrolyte Balance
Changes in the function of neuropeptide synthesizing cells within the suprachiasmatic nucleus (SCN), the site of the predominant circadian pacemaker, may underlie the disturbance of rhythms observed during ageing. Arginine vasopressin (AVP) is synthesized by nearly one-third of SCN neurones in the rat. This peptide has predominantly excitatory actions within the SCN mediated by V(1)-type receptors; the extent to which the V(1a) and/or V(1b) receptor subtypes are involved in SCN functions remains to be determined. The present study used isotopic in situ hybridization histochemistry to examine the effects of ageing on expression of mRNAs for AVP and V(1a) in the SCN and for V(1b) in the SCN and supraoptic nucleus (SON) of male rats kept under a 12 : 12 h light/dark cycle. Analysis of film autoradiographs from young adult (2-3-month-old; n = 40) or aged (19-20-month-old; n = 40) animals, at eight time points across the light/dark cycle, revealed an equivalent pattern and amplitude for the diurnal rhythm of AVP mRNA in the SCN of the young adult and aged groups. Both groups also displayed a significant diurnal rhythm in the expression of V(1a) receptor mRNA; however, the amplitude of this rhythm was reduced in the aged group, due to increased levels during the light phase and early part of night. Although the expression of V(1b) mRNA did not display a significant diurnal rhythm within the SCN or SON, persistently elevated levels for V(1b) mRNA were observed in the aged group at both sites.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Circadian Rhythm
- In Situ Hybridization
- Male
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Receptors, Vasopressin
- Suprachiasmatic Nucleus
- Supraoptic Nucleus
Kidneys of new-born animals are resistant to arginine vasopressin (AVP). The ability of the hormone to regulate water permeability of the collecting duct can be seen from weaning period, probably due to the maturation of the intracellular signaling pathway. The purpose of the present work was to investigate the effect of V2 receptor agonist dDAVP on the water permeability of OMCD basolateral membrane in 10-, 22- and 60-day old Wistar rats. We also estimated ontogenetic gene expression of AQP2, AQP3, AQP4 and V2 receptor. Osmotic water permeability (Pf) of the basolateral membrane of microdissected OMCD was measured under control conditions and after incubation with the agonist V2 receptor desmopressin (dDAVP; 10(-7) M). Water permeability in 10- and 22-day old rats under control conditions were significantly higher than in adults. Desmopressin stimulated significant increase of this parameter in 22-day old pups (Pf = = 125 /- 4.85; Pf = 174 /- 8.2 microns/s, p < 0.001) and adult rats (Pf = 100.5 /- 7.38; Pf = 178.8 /- 9.54 microns/s, p < 0.001). Osmotic water permeability of the OMCD basolateral membrane in 10-day old rats does not depend on dDAVP (Pf = 172.5 /- 23.8; Pf = 164.8 /- 34 microns/s). With the RT-PCR, we observed a gradual increase of AQP2 and V2 receptor genes expression during postnatal ontogenesis. The gene expression of AQP3 and AQP4 remained unchanged during postnatal ontogenesis. In general, the water permeability of the OMCD basolateral membrane of rats can be stimulated by AVP since the 22nd day of postnatal life. The water permeability of the OMCD basolateral membrane under control conditions gradually decreased during postnatal development, while gene expression of AQP3 and AQP4 was unchanged. The mechanism of this decrease remains to be established.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Aquaporin 6
- Aquaporins
- Cell Membrane Permeability
- Deamino Arginine Vasopressin
- Female
- Kidney Medulla
- Kidney Tubules, Collecting
- Male
- Osmosis
- Rats
- Rats, Wistar
- Receptors, Vasopressin
- Renal Agents
- Water
Hyponatremia occurs not infrequently in hypopituitarism. Arginine vasopressin (AVP)-induced impaired water excretion is found in patients with hypopituitarism and experimental models of glucocorticoid deficiency. The present study was undertaken to determine whether augmented release of AVP is involved in the development of hyponatremia in elderly subjects with secondary adrenal insufficiency. Forty patients with ACTH-deficient, secondary adrenal insufficiency were examined. They were divided into three groups according to the age at which diagnosis was ascertained (group A <20 Years, group B 20-64 Years, and group C>or=65 Years). Hyponatremia was more manifest in the elderly group than in the other two groups, serum sodium (Na) levels being 124.7 mmol/l in the elderly group, a value significantly less than 141.5 and 133.5 mmol/l in groups A and B. Plasma AVP levels seemed likely to be high compared with the respective hypo-osmolality in plasma in the elderly group, as plasma AVP levels were 1.7 pmol/l despite a mean plasma osmolality of 259 mmol/kg. Such an alteration was less clear in group B and was not found in group A. Therefore, elevation of plasma AVP was apparent in the elderly patients. Hydrocortisone replacement promptly normalized serum Na levels from 125 to 142 mmol/l (P<0.01) and reduced plasma AVP levels from 1.7 to 0.9 pmol/l (P<0.05), which were comparable to the respective plasma osmolality in the elderly patients. These results indicate that non-suppressible release of AVP is crucially involved in the impaired water excretion and hyponatremia seen in elderly patients with secondary adrenal insufficiency compared with the younger patients, and that exaggerated release of AVP becomes manifest as the subjects grow older.
MeSH Terms
- Adolescent
- Adrenal Insufficiency
- Adrenocorticotropic Hormone
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Hormones
- Humans
- Hydrocortisone
- Hyponatremia
The process of normal aging is accompanied by changes in sleep-related endocrine activity. During aging, an increase in cortisol at its nadir and a decrease in renin and aldosterone concentration occur. In aged subjects, more time is spent awake and slow-wave sleep is reduced: there is a loss of sleep spindles and accordingly a loss of power in the sigma frequency range. Previous studies could show a close association between sleep architecture, especially slow-wave sleep, and activity in the glutamatergic and GABAergic system. Furthermore, recent studies could show that the natural N-methyl-D-aspartate (NMDA) antagonist and GABA(A) agonist Mg(2 ) seems to play a key role in the regulation of sleep and endocrine systems such as the HPA system and renin-angiotensin-aldosterone system (RAAS). Therefore, we examined the effect of Mg(2 ) in 12 elderly subjects (age range 60-80 years) on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. A placebo-controlled, randomised cross-over design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg(2 ) was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days. At the end of each interval, a sleep EEG was recorded from 11 p.m. to 7 a.m. after one accommodation night. Blood samples were taken every 30 min between 8 p.m. and 10 p.m. and every 20 min between 10 p.m. and 7 a.m. to estimate ACTH, cortisol, renin and aldosterone plasma concentrations, and every hour for arginine-vasopressin (AVP) and angiotensin 11 (ATII) plasma concentrations. Mg(2 ) led to a significant increase in slow wave sleep (16.5 /- 20.4 min vs. 10.1 /- 15.4 min, < or =0.05), delta power (47128.7 microV(2) 21417.7 microV(2) vs. 37862.1 microV(2) /- 23241.7 microV(2), p < or =0.05) and sigma power (1923.0 microV(2) 1111.3 microV(2) vs. 1541.0 microV(2) 1134.5 microV(2), p< or =0.05 ). Renin increased (3.7 /- 2.3 ng/ml x min vs. 2.3 /- 1.0 ng/ml x min, p < 0.05) during the total night and aldosterone (3.6 /- 4.7 ng/ml x min vs. 1.1 /- 0.9 ng/ml x min, p < 0.05) in the second half of the night, whereas cortisol (8.3 /- 2.4 pg/ml x min vs. 11.8 /- 3.8 pg/ml x min, p < 0.01) decreased significantly and AVP by trend in the first part of the night. ACTH and ATII were not altered. Our results suggest that Mg(2 ) partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging. The similarities of the effect of Mg(2 ) and that of the related electrolyte Li furthermore supports the possible efficacy of Mg(2 ) as a mood stabilizer.
MeSH Terms
- Administration, Oral
- Adrenocorticotropic Hormone
- Aged
- Aging
- Aldosterone
- Angiotensin II
- Arginine Vasopressin
- Cross-Over Studies
- Dietary Supplements
- Drug Administration Schedule
- Electroencephalography
- Female
- Hormones
- Humans
- Hydrocortisone
- Magnesium Compounds
- Male
- Middle Aged
- Renin
- Sleep
- Sleep Stages
- Sleep Wake Disorders
- Treatment Outcome
The neurohypophyseal hormones arginine-vasopressin (AVP) and oxytocin (OT) are produced in the neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nucleus and in the much smaller cells of the suprachiasmatic (SCN) nucleus. The SON is the main source of plasma AVP. Part of the AVP and OT neurons of the PVN join the hypothalamo-neurohypophyseal tract, whereas others send projections to the median eminence or various brain areas, where AVP and OT are involved in a number of central functions as neurotransmitters/neuromodulators. AVP and OT from the PVN can also regulate via the autonomous innervation endocrine glands and fat tissue. OT is produced for a major part in the PVN but some OT neurons are present in the SON. Moreover, both AVP and OT containing neurons are observed in the "accessory nuclei", i.e. islands situated between the SON and PVN. The SCN is the biological clock, and the number of AVP expressing neurons in the SCN shows both diurnal and seasonal rhythms. In addition to these hypothalamic areas, AVP and OT may be found to a lesser extent in some other brain areas, such as the bed nucleus of the stria terminalis, diagonal band of Broca, nucleus basalis of Meynert, lateral septal nucleus, globus pallidus and the anterior amygdaloid nucleus, as well as in the peripheral tissues. The AVP and OT containing neurons should not be considered as one system. Prominent functional differences exist between the different nuclei. The heterogeneity also becomes clear from the marked differences in the neurohypophyseal peptides containing neurons of the SON, PVN and SCN during aging, and in the most prevalent age-related neurodegenerative diseases, i.e. Alzheimer's disease (AD). For those reasons, we will discuss the SON, PVN and SCN separately.
MeSH Terms
- Aging
- Alzheimer Disease
- Animals
- Arginine Vasopressin
- Humans
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Pituitary Hormones, Posterior
- Supraoptic Nucleus
Aminopeptidases (APs) are important regulators of peptides directly involved in water homeostasis such as angiotensins (Ang) and vasopressin (AVP). Sex differences in water balance and differences in the effects of gonadal steroids on osmotic stimulation of vasopressin secretion have been reported. Since sex steroids may be involved, the gonadotropin response to osmotic stimuli may be different between males and females. The purpose of this study was to determine the behavior of angiotensinases, vasopressin-degrading activity and gonadotropin-releasing hormone (GnRH)-degrading activity in the cortex and medulla of the kidney of dehydrated male and female rats. In the renal cortex, our results demonstrated an increase in Ang III-degrading activity in dehydrated males but not in females. This response may lead to an increased formation of Ang IV. This occurs with an increase in AspAP activity (which metabolizes Ang I to des-Asp(1)-Ang I), with no changes in Ang II-degrading activity and also with increased levels of AVP-degrading activity in dehydrated animals. These results may suggest an increased cortical blood flow due to enhanced formation of Ang IV together with reduced availability of the vasoconstrictor agents Ang II and AVP in the renal cortex of dehydrated males. The results obtained in the renal medulla suggest the inhibition of the metabolism of Ang I to des-Asp(1)-Ang I, together with a reduced metabolism of Ang II and AVP in dehydrated males but not in females. These results suggest a prolonged action of Ang II and AVP, which could stimulate sodium and water reabsorption in the medulla of dehydrated males. Changes in APs after dehydration occur preferentially in males, which may explain in part the reported sex differences in water homeostasis. The present results suggest a physiologically relevant role for AP activities in water homeostasis.
MeSH Terms
- Aging
- Aminopeptidases
- Animals
- Dehydration
- Female
- Homeostasis
- Kidney Cortex
- Kidney Medulla
- Male
- Rats
- Rats, Sprague-Dawley
- Sex Characteristics
- Water
Basal hypothalamic-pituitary-adrenal (HPA) function is characterised by pulses of corticosterone secretion followed by a transient refractory period when the axis appears to be inhibited. In females pulses of corticosterone secretion occur approximately once per hour with variation in pulse amplitude underlying a diurnal rhythm. Males show smaller pulses of secretion which become widely spaced during the early light phase nadir. Pulsatility is altered by genetic programming, early life experiences and reproductive status. Activation of the HPA axis during adjuvant induced arthritis results in an increase in the pulse frequency. This is associated with a marked change in hypothalamic gene expression with a diminution of CRH mRNA and a marked increase of AVP mRNA which becomes the predominant HPA secretagogue.
MeSH Terms
- Adrenal Glands
- Aging
- Animals
- Animals, Newborn
- Corticosterone
- Hypothalamus
- Pituitary Gland, Anterior
- Stress, Physiological
Postmortem examinations of the hypothalamus of patients with autosomal dominant neurohypophyseal diabetes insipidus (adNDI), which have been reported only on persons dying between the ages of 37-87 yr, reveal the presence of the arginine vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the expected AVP-producing magnocellular neurons. To determine whether the clinical course of adNDI is compatible with the hypothesis that the neuropathologic findings are attributable to a progressive loss of magnocellular neurons beginning in early life, we performed posterior pituitary magnetic resonance imaging and water deprivation tests, including plasma ACTH measurements, on 17 affected members of a kindred with the deltaE47 neurophysin mutation whose ages ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr) underwent these tests as controls. All six children undergoing magnetic resonance imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of nine affected adults showed an absent or barely visible PPHS, whereas eight of nine age-matched nonaffected adults produced a normal size PPHS. During water deprivation tests, infants concentrated their urine normally, and a 3-month-old infant produced a high plasma AVP level of 15.7 pmol/liter. By school age, affected children were no longer able to concentrate their urine or prevent hypernatremia. Affected adults became dehydrated; their median plasma AVP level was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P = 0.008). These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.
MeSH Terms
- Adult
- Aging
- Child
- Child, Preschool
- Diabetes Insipidus, Neurogenic
- Female
- Genes, Dominant
- Humans
- Infant
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Mutation
- Neurophysins
- Pedigree
- Pituitary Gland, Posterior
- Vasopressins
- Water Deprivation
The mechanisms underlying the prevention of age-related polyuria by chronic food restriction were investigated in female WAG/Rij rats. The decreased osmolality of renal papilla observed in senescent rats was not corrected by food restriction. A reduced urea content in the inner medulla of senescent rats, fed ad libitum or food-restricted, was suggested by the marked decrease in expression of UT-A1 and UT-B1 urea transporters. Aquaporin-2 (AQP2) downregulation in the inner medulla of senescent rats was partially prevented by food restriction. Both AQP2 and the phosphorylated form of AQP2 (p-AQP2), the presence of which was diffuse within the cytoplasm of collecting duct principal cells in normally fed senescent rats, were preferentially targeted at the apical region of the cells in food-restricted senescent animals. Plasma vasopressin (AVP) was similar in 10- and 30-mo-old rats fed ad libitum, but was doubled in food-restricted 30-mo-old rats. This study indicates that 1) kidney aging is associated with a marked decrease in AQP2, UT-A1, and UT-B1 expression in the inner medulla and a reduced papillary osmolality; and 2) the prevention of age-related polyuria by chronic food restriction occurs through an improved recruitment of AQP2 and p-AQP2 to the apical membrane in inner medulla principal cells, permitted by increased plasma AVP concentration.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Aquaporin 6
- Aquaporins
- Carrier Proteins
- Cell Polarity
- Eating
- Female
- Kidney
- Kidney Medulla
- Kidney Tubules
- Membrane Glycoproteins
- Membrane Transport Proteins
- Osmolar Concentration
- Phosphorylation
- Polyuria
- Protein Transport
- Rats
- Urine
- Vasopressins
- Water-Electrolyte Imbalance
To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested. Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of 125I- and 131I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V1a receptors were performed in young and old rats. RBF decreased by 43 /- 3% in 10-week SHR (9.2 /- 0.5 vs. 5.2 /- 0.3 ml x min(-1) x g(-1)), significantly more than 10-week WKY where RBF decreased by 35 /- 3% (9.6 /- 0.7 vs. 6.5 /- 0.5 ml x min(-1) x g(-1)) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 /- 5% in SHR and 23 /- 4% in WKY (p > 0.05). GFR decreased by 6 /- 3% (1.03 /- 0.04 vs. 0.96 /- 0.04 ml x min(-1) x g(-1), p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 /- 0.07 vs. 1.08 /- 0.04 ml x min(-1) x g(-1), p > 0.10). GFR decreased by 11 /- 10% in 40-week SHR and by 4 /- 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V1a receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05). The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V1a receptors.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Glomerular Filtration Rate
- Hemodynamics
- Infusions, Intravenous
- Male
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Reference Values
- Renal Circulation
- Vasoconstriction
- Vasoconstrictor Agents
The neurohypophysial peptides oxytocin (OT) and vasopressin (AVP) are well known for their role in reproductive functions and fluid balance regulation, respectively. During development, these peptides are thought to act as trophic factors on both peripheral and central structures. However, despite this early developmental function, the maturation of their secreting neurons remains poorly investigated. In this study, we have characterized the electrical and morphological characteristics displayed by OT and AVP supraoptic (SO) neurons between embryonic day 21 and postnatal day 20. Transient changes in passive membrane properties, correlated with a transient increase in the dendritic arborization, were observed at the beginning of the second postnatal week (PW2). The action potential matured mostly during PW1 and its threshold progressively hyperpolarized in parallel with the resting membrane potential. During PW1, SO neurons displayed unique characteristics with a low-threshold Ca(2 )-dependent depolarizing potential and a prominent hyperpolarization-activated current (I(h) ). This latter is involved in a depolarizing sag during hyperpolarization and an after hyperpolarizing potential following a depolarization. During this period, maintaining E(Cl) unchanged by the use of gramicidin-perforated patch recordings revealed excitatory GABAergic potentials, that became inhibitory during PW2, whilst glutamatergic potential appeared. The electrical activity was very erratic in young neurons and progressively differentiated in the typical firing observed in mature neurons (tonic and phasic for OT and AVP neurons, respectively) during PW2--3. These results show that the development of electrical properties of SO neurons is correlated with the maturation of their dendritic arborization.
MeSH Terms
- Action Potentials
- Aging
- Animals
- Animals, Newborn
- Cellular Senescence
- Differential Threshold
- Electrophysiology
- Embryo, Mammalian
- In Vitro Techniques
- Male
- Membrane Potentials
- Neurons
- Rats
- Supraoptic Nucleus
- Synapses
The present study was undertaken to determine whether urinary excretion of aquaporin-2 (AQP-2) participates in the involvement of arginine vasopressin (AVP) in hyponatremia less than 130 mmol/L in 33 elderly subjects (> or =65 yr old) during the last 5-yr period. Subjects were separated into euvolemic hyponatremia groups: 13 with hypopituitarism, 8 with syndrome of inappropriate secretion of antidiuretic hormone (SIADH), 8 with mineralocorticoid-responsive hyponatremia of the elderly, and 4 with miscellaneous diseases. Approximately 40% of those with hyponatremia was derived from hypopituitarism, but severe hyponatremia was found in the patients with SIADH and mineralocorticoid-responsive hyponatremia of the elderly. Plasma AVP levels remained relatively high despite hypoosmolality and were tightly linked with exaggerated urinary excretion of AQP-2 and antidiuresis in the 3 groups of patients, except for one miscellaneous one. An acute water load test verified the impairment in water excretion, because the percent excretion of the water load was less than 42% and the minimal urinary osmolality was not sufficiently diluted. Also, plasma AVP and urinary excretion of AQP-2 were not reduced after the water load. The inappropriate secretion of AVP was evident in the patients with SIADH and hypopituitarism, and hydrocortisone replacement normalized urinary excretion of AQP-2 and renal water excretion in those with hypopituitarism. In contrast, the appropriate antidiuresis seemed to compensate loss of body fluid in the patients with mineralocorticoid-responsive hyponatremia of the elderly, who lost circulatory blood volume by 7.3% (mean). Fludrocortisone acetate increased renal sodium handling and body fluid, resulting in the reduction in AVP release and urinary excretion of AQP-2 in mineralocorticoid-responsive hyponatremia of the elderly. These findings indicate that urinary excretion of AQP-2 may be a more sensitive measure of AVP effect on renal collecting duct cells than are plasma AVP levels, and that increased urinary excretion of AQP-2 shows exaggerated AVP-induced antidiuresis in hyponatremic subjects in the elderly. In addition, mineralocorticoid-responsive hyponatremia of the elderly has to be carefully differentiated from SIADH in elderly subjects.
MeSH Terms
- Aged
- Aging
- Aldosterone
- Aquaporin 2
- Aquaporin 6
- Aquaporins
- Arginine Vasopressin
- Blood Volume
- Diuresis
- Female
- Fludrocortisone
- Humans
- Hydrocortisone
- Hyponatremia
- Hypopituitarism
- Inappropriate ADH Syndrome
- Kidney
- Male
- Mineralocorticoids
- Renin
- Sodium
Aging leads to many changes in the expression of circadian rhythms, including reduced amplitude, altered relationship to the environmental illumination cycle, and reduced sensitivity to phase resetting signals. Neuropeptide synthesizing neurons in the suprachiasmatic nucleus (SCN), the principal circadian pacemaker in mammals, play a role in regulating pacemaker function and in coupling the pacemaker to overt circadian rhythms. Aging may alter the activity of neuropeptide neurons in the SCN, which could be reflected in changes in mRNA expression. Therefore, this study investigated whether aging alters the level or rhythm of expression of neuropeptide mRNAs in the SCN of male Syrian hamsters, a well established model for the study of age-related changes in circadian rhythms. Three age groups of hamsters (young [3--5 months old], middle-aged [12--15 months old] and old [19--22 months old] were sacrificed at five times of day. Their brains were dissected and sections through the suprachiasmatic nucleus were prepared and used for in situ hybridization for mRNAs for vasoactive intestinal peptide (VIP), arginine vasopressin (AVP) and somatostatin (SS). Aging selectively decreased the SCN expression of VIP mRNA without affecting AVP mRNA or SS mRNA. Also, only AVP mRNA expression exhibited a robust 24-h rhythm, in contrast to previous findings in other species that VIP mRNA and SS mRNA, as well as AVP mRNA, exhibit 24-h rhythms in the SCN. The present findings suggest that age-related reductions in VIP mRNA expression may contribute to the alterations in entrainment and attenuated sensitivity to phase resetting signals that are characteristic of aging. Furthermore, the results demonstrate that neuropeptide gene expression in the SCN is differentially regulated by aging and varies among species.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Brain Chemistry
- Circadian Rhythm
- Cricetinae
- Gene Expression
- In Situ Hybridization
- Male
- Mesocricetus
- RNA, Messenger
- Somatostatin
- Suprachiasmatic Nucleus
- Vasoactive Intestinal Peptide
Hypothyroid pups were obtained by adding methimazole in the mother's drinking water from day 15 of gestation and sacrificed at 4, 8 or 15 days. Circulating corticosterone decreased at all ages, while CBG concentrations diminished at day 4, increased at day 8 and did not change at day 15 in hypothyroid rats. As opposed to controls, plasma ACTH concentrations decreased steadily with age while there was an accumulation of ACTH in the anterior pituitary of hypothyroid 15-day-old rats. Anterior pituitary POMC contents were unaffected by the treatment. In the hypothalamic PVN, CRF mRNA levels in the total population of CRF-synthesizing cells and in the CRF /AVP subpopulation were below those of controls whatever the age considered while AVP mRNA in the CRF /AVP subpopulation did not change at day 4 and decreased at day 8 and 15 in hypothyroid animals. Both the number of cell bodies expressing detectable levels of CRF mRNA and the percentage of CRF and AVP colocalization decreased at day 4 and were unchanged thereafter. CRF and AVP immunoreactivity in the zona externa of the median eminence increased with age but was not affected by methimazole treatment. The concentration of AVP mRNA in the magnocellular cell bodies of the PVN and the SON as well as AVP immunoreactivity in the zona interna of the median eminence were not changed by the treatment at days 4 and 8. In hypothyroid 15-day-old rats, SON AVP mRNA increased, AVP immunoreactivity decreased while plasma osmolality was enhanced. In conclusion, our data demonstrate that experimental hypothyroidism impairs specifically the maturation of hypothalamic parvocellular CRF and AVP gene expression during the stress hyporesponsive period. These observations suggest that the physiological peak in plasma thyroxine concentrations that occur between day 8-12 may participate in the maturation of hypothalamic CRF- and AVP-synthesizing cells.
MeSH Terms
- Administration, Oral
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Corticosterone
- Corticotropin-Releasing Hormone
- Disease Models, Animal
- Female
- Gene Expression Regulation, Developmental
- Hypothalamo-Hypophyseal System
- Hypothyroidism
- Methimazole
- Paraventricular Hypothalamic Nucleus
- Pituitary Gland, Anterior
- Pituitary-Adrenal System
- Pregnancy
- Prenatal Exposure Delayed Effects
- Pro-Opiomelanocortin
- Rats
- Rats, Sprague-Dawley
- Supraoptic Nucleus
- Thyrotropin
- Transcortin
The dorsolateral supraoptic nucleus (dl-SON) is the main production site of plasma arginine vasopressin (AVP). Plasma AVP levels and the activity of AVP neurons in humans are higher in males than in premenopausal females. On the other hand, an increased activity of AVP neurons becomes prominent in postmenopausal women who have strongly decreased estrogen levels. As estrogens are presumed to inhibit AVP production in a receptor-mediated way, we studied estrogen receptor (ER) alpha and beta immunoreactivity in the dl-SON. Hypothalami of 34 controls were subdivided into 4 groups within a 50-yr boundary (young men, young women, elderly men, and elderly women). The AVP part of the dl-SON of young women contained 50 times more neurons with ERbeta nuclear staining than that in young men and 250 times more than that in elderly women. In addition, young women also showed more ERbeta cytoplasmic staining than young men and elderly women. In contrast to the ERbeta immunoreactivity, no differences were found in the number of ERalpha-positive neurons in the 4 groups, but the age and sex pattern of ERalpha staining was basically opposite that of ERbeta. Significant correlations between the percentage of ERbeta- and ERalpha-positive and -negative AVP neurons and age were found in women, but not in men. Our data demonstrate for the first time a strong decrease of ERbeta and an increase of ERalpha immunoreactivity in AVP neurons of the dl-SON of postmenopausal women. Both receptor changes are proposed to participate in the activation of the AVP neurons in postmenopausal women.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Antibody Specificity
- Arginine Vasopressin
- Cell Nucleus
- Cytoplasm
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Female
- Humans
- Image Processing, Computer-Assisted
- Immunohistochemistry
- Male
- Middle Aged
- Neurons
- Paraffin Embedding
- Receptors, Estrogen
- Sex Characteristics
- Supraoptic Nucleus
- Tissue Fixation
To examine potential intracellular signalling abnormalities of endothelin-1 (ET-1) and vasopressin (AVP) which may contribute to blood pressure elevation, contractility and inositol phosphate levels in intact arteries and calcium transients in vascular smooth muscle cells were investigated after stimulation with these peptides in pre-hypertensive 5 week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats. Contractility of aorta in response to ET-1, AVP and norepinephrine (NE) was blunted in SHR relative to WKY. Contraction of mesenteric resistance arteries induced by ET-1 was similar in both groups, whereas sensitivity in response to NE and AVP was greater in SHR. Basal inositol phosphate in aorta and mesenteric arteries was elevated in SHR, but ET-1 and AVP-stimulated inositol phosphate responses were similar in both groups. Calcium transients induced by ET-1 and AVP in vascular smooth muscle cells were similar in young SHR and WKY. In contrast, in adult rats inositol phosphate responses to ET-1 were blunted in aorta of SHR, but were normal in mesenteric arteries. Inositol phosphate responses to AVP were similar in both rat strains of rats both in aorta and mesenteric arteries except for accumulation of inositol trisphosphate, which was enhanced in mesenteric arteries of SHR. Calcium mobilization in vascular smooth muscle cells from adult SHR also exhibited enhanced responses to AVP. In conclusion, in young SHR, blunted ET-1 and AVP-induced contraction in aorta and enhanced AVP-induced mesenteric artery contraction are associated with normal inositol phosphate production and calcium mobilization. Signal transduction in response to ET-1 and AVP is depressed in aorta of pre-hypertensive SHR after the step of inositol phosphate generation and calcium mobilization. Resistance vessel reactivity to AVP is enhanced in young SHR at steps following inositol phosphate generation and calcium mobilization. These results argue against a role of ET-1, but suggest the possible involvement of AVP in the development of this model of genetic hypertension.
MeSH Terms
- Aging
- Animals
- Antibodies
- Aorta
- Arginine Vasopressin
- Blood Pressure
- Body Weight
- Calcium
- Cells, Cultured
- Dose-Response Relationship, Drug
- Endothelin-1
- Male
- Mesenteric Arteries
- Muscle, Smooth, Vascular
- Norepinephrine
- Phosphatidylinositols
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Signal Transduction
- Tritium
- Type C Phospholipases
- Vasoconstriction
- Vasoconstrictor Agents
The suprachiasmatic nucleus (SCN) is the dominant circadian pacemaker in mammals. To understand better the ontogeny of mouse SCN and the role of the pacemaker in peptide expression, the authors examined the distribution of cells that were immunoreactive for vasopressin (AVP) or vasoactive intestinal polypeptide (VIP) in wild type and Clock mutant mice at two developmental stages. Clock homozygous mice failed to show the dramatic increase in the number of VIP-immunoreactive (VIP-ir) neurons from postnatal day 6 (P6) to P30 that was found in the SCN of wild type mice. The number of AVP-ir neurons was relatively constant in the postnatal SCN but was significantly reduced in Clock/Clock mice. The effects of the Clock mutation varied with position in the SCN for both peptides. Densitometry of immunolabeled brains indicated that the Clock mutation reduced AVP expression specifically in the SCN and not in other brain areas. The SCN did not significantly change shape or size with age or Clock genotype. Taken together, these results indicate that the neonatal mouse SCN has its full complement of cells, some of which are not yet mature in their neuropeptide content. Furthermore, the observation that the Clock mutation appears to act on a subset of AVP and VIP cells suggests heterogeneity within these cell classes in the SCN.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- CLOCK Proteins
- Female
- Male
- Mice
- Mice, Inbred Strains
- Neurons
- Neuropeptides
- Suprachiasmatic Nucleus
- Thalamus
- Tissue Distribution
- Trans-Activators
- Vasoactive Intestinal Peptide
The effect of age on the stimulatory control exerted by cholinergic- and angiotensin II (ANG II)-mediated neurotransmission on arginine vasopressin (AVP) secretion was evaluated by measuring and comparing the AVP responses to the administration of either the cholinesterase inhibitor physostigmine (13.5 micrograms/kg in 50 mL normal saline infused in 10 minutes) or ANG II (increasing doses of 4, 8, and 16 micrograms/kg/min, each dose for 20 min) in 8 younger (23-37 years), 8 middle age (42-60 years), and 8 older (63-79 years) healthy male subjects. Both drugs induced significant increments in plasma AVP levels in the youngest group, with mean peak levels 4.8 times higher than baseline at 20 minutes after the beginning of physostigmine infusion and 1.5 times higher than baseline at 60 minutes after the beginning of ANG II infusion. Similar responses were observed in the middle age group. Basal AVP levels in older subjects were similar to those observed in the other groups. However, the AVP increases induced by physostigmine (mean peak was 9 times higher than baseline) and ANG II (mean peak was 2.2 times higher than baseline) were significantly higher in the oldest group than in the other groups. These data suggest age-related enhancement of the stimulatory regulation exerted by cholinergic- and ANG II-mediated neurotransmission on AVP secretion.
MeSH Terms
- Adult
- Aged
- Aging
- Angiotensin II
- Arginine Vasopressin
- Cholinesterase Inhibitors
- Clinical Chemistry Tests
- Humans
- Male
- Middle Aged
- Physostigmine
- Vasoconstrictor Agents
The ageing process has been shown to have a profound impact on the hypothalamo-neurohypophysial system (HNS) and the hypothalamo-pituitary-adrenocortical (HPA) axis in humans as well as in rodents. Therefore, in this study, the intracerebral and peripheral release patterns of both vasopressin and oxytocin have been studied in aged male Wistar rats under basal conditions and in response to ethologically relevant stressors, using intracerebral microdialysis and chronic blood sampling techniques, respectively. Approximately a twofold higher basal release of arginine vasopressin (AVP) within the hypothalamic paraventricular nucleus (PVN), but not within the supraoptic nucleus (SON), was found in aged rats, whereas basal oxytocin (OXT) release did not differ in comparison with young rats. With increasing age the rise in intra-PVN release of both AVP and OXT was blunted in response to forced swimming. In contrast, the intra-SON release of AVP was unrelated to age. Simultaneously recorded basal secretion of both AVP and OXT from the neurohypophysis into blood was increased in aged rats, with a blunted OXT response to swim stress. Opposed to that, plasma AVP levels remained unchanged in both groups. Basal plasma levels of corticotropin (ACTH) and corticosterone were elevated in aged rats, whereas stress-elicited ACTH and corticosterone responses were indistinguishable. These results indicate age-related changes in the HNS and HPA axis with an enhanced basal activity opposed to a blunted response to stressors with increasing age. The increased basal release of AVP within the PVN suggests a role of intracerebral AVP in age-associated alterations of HPA axis regulation.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Catheterization
- Corticosterone
- Hypertonic Solutions
- Hypothalamo-Hypophyseal System
- Isotonic Solutions
- Jugular Veins
- Lactic Acid
- Male
- Microdialysis
- Osmotic Pressure
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Pituitary-Adrenal System
- Rats
- Rats, Wistar
- Ringer's Solution
- Stress, Physiological
- Supraoptic Nucleus
- Swimming
- Vasopressins
Circadian rhythm disturbances are frequently present in Alzheimer disease (AD). In the present study, we investigated the expression of vasopressin (AVP) mRNA in the human suprachiasmatic nucleus (SCN). The in situ hybridization procedure on formalin-fixed paraffin-embedded material was improved to such a degree that we could, for the first time, visualize AVP mRNA expressing neurons in the human SCN and carry out quantitative measurements. The total amount of AVP mRNA expressed as masked silver grains in the SCN was 3 times lower in AD patients (n = 14; 2,135 /- 597 microm2) than in age- and time-of-death-matched controls (n = 11; 6,667 /- 1466 microm2) (p = 0.003). No significant difference was found in the amount of AVP mRNA between AD patients with depression (n = 7) and without depression (n = 7) (2,985 /-1103 microm2 and 1,285 /- 298 microm2, respectively; p = 0.38). In addition, the human SCN AVP mRNA expressing neurons showed a marked day-night difference in controls under 80 years of age. The amount of AVP mRNA was more than 3 times higher during the daytime (9,028 /- 1709 microm2, n = 7) than at night (2,536 /- 740 microm2, n = 4; p = 0.02), whereas no clear diurnal rhythm of AVP mRNA in the SCN was observed in AD patients. There was no relationship between the amount of AVP mRNA in the SCN and age at onset of dementia, duration of AD and the neuropathological changes in the cerebral cortex. These findings suggest that the neurobiological basis of the circadian rhythm disturbances that are responsible for behavioral rhythm disorders is located in the SCN. It also explains the beneficial effects of light therapy on nightly restlessness in AD patients.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Circadian Rhythm
- Depression
- Female
- Gene Expression
- Humans
- In Situ Hybridization
- Male
- Middle Aged
- RNA, Messenger
- Severity of Illness Index
- Suprachiasmatic Nucleus
Six young (mean s.e., 5.3 /- 0.8 years, 445 /- 13 kg bwt) and 6 old (22.0 /- 0.4 years, 473 /- 18 kg bwt) Standardbred and Thoroughbred mares were used to test the hypothesis that age would alter the endocrine response to exercise. All of the mares were unconditioned but accustomed to the laboratory, to standing quietly and running on a treadmill, and to the standardised incremental exercise test (SET) used in the experiment. Two weeks prior to the experiment, each horse underwent a SET to determine maximal oxygen uptake (VO2max) and the speeds to be used in the actual experiment. A second graded exercise test (GXT) was performed without instrumentation for the measurement of plasma renin activity (PRA) and the plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), aldosterone (ALDO), and endothelin-1 (ET-1). Blood samples (30 ml) were collected at rest and at the end of each one minute step of the exercise test. Plasma concentrations of hormones were measured using radioimmunoassay kits. There were no differences (P > 0.05) between old vs. young mares for resting PRA (2.2 /- 0.3 vs. 1.5 /- 0.3 ng/ml/h), or the plasma concentrations of ANP (10.0 /- 0.9 vs. 10.7 /- 0.6 pg/ml); AVP (0.7 0.7 vs. 1.4 /- 0.4 pg/ml); ALDO (39.2 /- 10.3 vs. 22.7 /- 4.6 pg/ml); or ET-1 (0.23 /- 0.04 vs. 0.18 /- 0.03 pg/ml). Exercise significantly increased PRA and the concentrations of ANP, AVP, and ALDO in both groups of horses; however, ET-1 was not altered (P > 0.05) by exercise in either group. There were differences (P < 0.05) between means obtained from the old and young groups for PRA (5.4 /- 0.6 vs. 3.9 /- 0.8 ng/ml/h and the concentrations of ANP (14.5 /- 2.3 vs. 26.5 /- 9.0 pg/ml), AVP (13.6 /- 0.3 vs. 26.1 /- 13.9 pg/ml, and ALDO (76.8 /- 22.0 vs. 41.5 /- 4.9 pg/ml) measured in samples obtained at the speed eliciting VO2max. These data suggest that older horses have an age-altered endocrine response to exercise.
MeSH Terms
- Aging
- Aldosterone
- Animals
- Arginine Vasopressin
- Atrial Natriuretic Factor
- Endothelin-1
- Female
- Hormones
- Horses
- Oxygen Consumption
- Physical Conditioning, Animal
- Renin
The ageing process in animals and humans is thought to be accompanied by a gradual impairment of corticosteroid receptor function, which is reflected by increased pituitary-adrenocortical hormone secretion at baseline and a number of aberrant neuroendocrine function test results. The latter include the ACTH and corticosteroid responses to a combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) challenge. The excessive hormonal response to this test among aged individuals has been taken as indirect evidence of enhanced endogenous arginine vasopressin (AVP) release, which - together with peripherally administered CRH - is capable of overriding DEX-induced ACTH suppression. The current study was designed to explore the role of endogenous AVP in mediating excessive hypothalamic-pituitary-adrenocortical (HPA) activity in ageing. The combined DEX/CRH test was administered to aged (22-24 months old) Wistar rats and the effect of the AVP type 1 (V1) receptor antagonist, d(CH(2))(5)Tyr(Me)AVP, on ACTH release was studied. Infusion of the V1 receptor antagonist after DEX pretreatment and before CRH administration prevented the CRH-induced rise in ACTH secretion in comparison with vehicle-treated aged rats (area under the concentration-time curve: 699 /-479 versus 2896 /-759; P<0.01). This difference was absent in young (3 months old) control rats. In situ hybridization showed an increased number of AVP mRNA-expressing neurons in the parvocellular but not the magnocellular, portion of the hypothalamic paraventricular nucleus in DEX-pretreated aged rats. The number and synthetic activity of parvocellular neurons expressing CRH mRNA was also increased. We have concluded that the increased HPA activity in aged rats involves enhanced synthesis and release of AVP from parvocellular neurons, possibly secondary to impaired corticosteroid receptor function.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Blood Pressure
- Corticosterone
- Corticotropin-Releasing Hormone
- Dexamethasone
- Heart Rate
- Hypothalamo-Hypophyseal System
- Male
- RNA, Messenger
- Rats
- Rats, Wistar
- Vasopressins
Systemic lupus erythematosus (SLE) is a spontaneously occurring, chronic autoimmune disease that can manifest neuropsychiatric abnormalities. The pathways mediating these central changes are not known; however, neuroendocrine alterations associated with inflammation may play a role. Predisposition to and progression of autoimmune disease has been associated with altered hypothalamic-pituitary-adrenal (HPA) function and inflammation has been reported to alter hypothalamic regulation of HPA responses. We investigated whether disease progression in a murine model of systemic lupus erythematosus (MRL / . MRL lpr/lpr) resulted in altered expression of HPA regulatory peptides at the level of the hypothalamus and how these alterations related to circulating levels of corticosterone, corticosterone binding globulin, and autoantibody titers. We report that as MRL / and MRL lpr/lpr mice age and circulating levels of autoantibodies increase, there is a decrease in hypothalamic CRH mRNA expression and finally an increase in AVP mRNA expression. We also report that associated with increased autoantibody levels, disease progression, and altered hypothalamic peptide expression there is an increase in circulating levels of corticosterone and a trend for levels of corticosterone binding globulin to decrease. Our data complement previous observations of altered peptidergic regulation of the HPA axis and increased HPA activity during chronic inflammation in exogenously induced rodent models of chronic inflammation and indicate that similar processes may occur in spontaneous murine models of SLE.
MeSH Terms
- Aging
- Animals
- Carrier Proteins
- Corticosterone
- DNA
- Disease Progression
- Enzyme-Linked Immunosorbent Assay
- Hypothalamo-Hypophyseal System
- Hypothalamus
- In Situ Hybridization
- Lupus Erythematosus, Systemic
- Male
- Mice
- Mice, Inbred MRL lpr
- Neuropeptides
The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the presence of sex differences in the vasopressinergic and oxytocinergic systems. The present study was aimed at determining whether the sizes of AVP and OT neurons in the human SON and PVN show sex differences, as earlier studies demonstrated that a change in neuronal size is a sensitive parameter for activity. The minimal and maximal diameters were determined to estimate the volumes of cell somata and cell nuclei in AVP and OT neurons stained with an antibody against human glycoprotein-(22-39), a part of the AVP precursor, and a monoclonal anti-OT antibody in 15 men and 17 women ranging in age from 29-94 yr. The AVP neurons appeared to be larger in young men than in young women (< or =50 yr old). In elderly women (>50 yr old) AVP cell size considerably exceeded that in young women. In elderly men AVP neurons were larger than in young men and elderly women, although these differences were not significant. In addition, AVP cell size correlated positively with age in women but not in men. No significant differences were found in the AVP cell nucleus volumes among all four groups studied. Sex differences in the size of the PVN vasopressin neurons were pronounced at the left side (P = 0.048) and absent at the right side (P = 0.368), indicating the presence of functional lateralization in this nucleus. No difference was found in any morphometric parameter of OT neurons in the PVN among the 4 groups studied. Thus, our data demonstrate sex differences in the size of the AVP neurons, and thus in their function, that are age and probably also side dependent and the absence of such changes in OT neurons in the PVN. These data provide a basis for the reported higher AVP plasma levels in men compared to women.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cell Size
- Female
- Humans
- Hypothalamus
- Immunohistochemistry
- Male
- Middle Aged
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Supraoptic Nucleus
- Vasopressins
In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic neurone activity was supposed to be present in the SON of men. Therefore we studied the size of the Golgi-apparatus (GA), which has been demonstrated previously to be a sensitive parameter for protein synthetic ability of neurones, in 15 men and 17 women ranging in age from 29 to 94 years. A polyclonal antibody against immunoaffinity purified MG-160, a sialoglycoprotein of the medial cisternae of the GA was applied on paraffin-embedded sections containing the dorsolateral SON (dl-SON) from which 90-95% of neurones are vasopressinergic. SON areas that contain oxytocin (OT) cells were excluded on the basis of adjacent sections stained with a monoclonal antibody against OT. By means of an image analysis system the size of the GA and the cellular profile area were determined in dl-SON neurones with a nucleolus. Our results showed indeed an age-dependent sex difference in the size of the GA that appeared to be twice as large in young men (< or = 50 years old) than in young women of the same age. The size of the GA increased with age in women but not in men. In addition, the mean cell profile area, another measure for neuronal activity, was significantly larger in young men than in young women and was in old women larger than in young women. In conclusion, these data show the presence of a sex-dependent age-difference in the activity of vasopressinergic neurones in dl-SON which may relate to differences in AVP and sex hormone levels and kidney AVP receptors.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Arginine Vasopressin
- Female
- Golgi Apparatus
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Neurons
- Sex Factors
- Supraoptic Nucleus
Male rats possess twice as many cells that express arginine-vasopressin (AVP) in the bed nucleus of the stria terminalis (BST) and centromedial amygdala (CMA) as do females. This sex difference may arise from sex differences in the induction of AVP expression in galanin (GAL)-expressing cells, which themselves do not differ in number between males and females. To test whether AVP expression could arise from a single pool of galaninergic cells, we determined whether the cell birth profile of GAL-immunoreactive (ir) cells was similar to that of AVP-ir cells. Dams were injected with the cell birth marker bromodeoxyuridine (BrdU) on one of seven gestational dates, ranging from embryonic day 11 (E11) to E17. The resulting offspring were sacrificed at 3 months of age. Processing their brains for the presence of either GAL and BrdU, or AVP and BrdU immunoreactivity revealed that in both the BST and CMA, the majority of GAL-ir and AVP-ir cells were labeled with BrdU on E12 and E13. In contrast, most other cells in the same region were labeled on E14 and E15. The similarity in the timing of cell birth of the GAL-ir and AVP-ir cells is consistent with the idea that GAL-ir cells in the BST/CMA constitute a single pool of cells that may be induced to express AVP during development.
MeSH Terms
- Aging
- Amygdala
- Animals
- Arginine Vasopressin
- Biomarkers
- Embryonic and Fetal Development
- Female
- Galanin
- Gestational Age
- Male
- Nerve Fibers
- Neurons
- Phenotype
- Rats
- Rats, Sprague-Dawley
- Sex Characteristics
- Thalamus
Levels of hypophysial portal arginine-vasopressin (AVP), plasma ACTH and plasma corticosterone (B) were measured in four and 24 month old Fischer 344 rats. Portal levels of AVP were lower in older rats whereas plasma ACTH levels were elevated. Older rats given adrenalectomies with physiologic replacement doses of B exhibited levels of AVP, but not ACTH, which were comparable to that observable in younger rats. The findings suggest that altered AVP, but not ACTH, can be accounted for by higher B levels which are commonly demonstrable in aging rats.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Brain Chemistry
- Corticosterone
- Corticotropin-Releasing Hormone
- Male
- Rats
- Rats, Inbred F344
- Stress, Physiological
Oxytocin (OT) stimulates corticotroph function in adult sheep, however, there is little information on OT synthesis and its potential involvement in hypothalamo-pituitary-adrenal (HPA) function in the fetus. The objectives of this study were to examine developmental changes in hypothalamic OT synthesis and to investigate the actions of OT on fetal corticotroph function. Hypothalami were removed at various stages of pre- and post-natal development. OT mRNA levels were measured using in situ hybridization. For in vitro studies, fetal pituitaries were removed on days 129 and 138 of gestation. Anterior pituitary cells were dispersed and cells were treated with different concentrations and combinations of OT, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and cortisol. OT mRNA was present in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by day 60 of gestation, and levels significantly increased at term. OT mRNA was present in parvocellular and magnocellular fields of the PVN. In vitro, OT stimulated adrenocorticotropin (ACTH) output in a dose-dependent fashion, but had no effect on cellular pro-opiomelanocortin (POMC) mRNA levels. There was no significant difference in corticotroph responsiveness to secretagogues between cells harvested at gestation day 129 or gestation day 138. Simultaneous exposure to CRH and OT stimulated increases in ACTH output that were significantly greater than for OT or CRH alone. However, no similar synergistic interaction existed between OT and AVP. Cortisol attenuated OT-stimulated ACTH output. In conclusion, hypothalamic OT mRNA increases at term and OT can stimulate ACTH output from fetal corticotrophs. Together, these data indicate that OT may be involved in the regulation of ACTH secretion in fetal sheep in late gestation.
MeSH Terms
- Adrenal Cortex
- Adrenocorticotropic Hormone
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Cells, Cultured
- Corticotropin-Releasing Hormone
- Drug Combinations
- Fetus
- Hydrocortisone
- Hypothalamo-Hypophyseal System
- Hypothalamus
- Oxytocin
- Pituitary Gland
- Pituitary-Adrenal System
- RNA, Messenger
- Sheep
During the course of aging both activation and degenerative changes are found in the human hypothalamus. Degeneration may start around middle-age in some neurotransmitter- or neuromodulator-containing neurons. For instance, a decreased number of vasoactive intestinal polypeptide (VIP) neurons was observed in the suprachiasmatic nucleus (SCN) of middle-aged males. The normal circadian fluctuations seen in the number of vasopressin (AVP) neurons in the SCN of young subjects diminished in subjects older than 50 years. Moreover, a sharp decline in cell number was found in the sexually dimorphic nucleus (SDN) after 50 years in males. On the other hand, many hypothalamic systems remain perfectly intact during aging like the oxytocin (OXT) neurons in the paraventricular nucleus (PVN). The AVP neurons in the PVN are activated during aging as appears from their increasing cell number. Also the corticotrophin-releasing hormone (CRH) neurons of the PVN are activated in the course of aging, as indicated by their increased number and their increased AVP coexpression. Part of the infundibular nucleus, the subventricular nucleus, contains hypertrophic neurokinin B neurons in postmenopausal women. It can be concluded that a multitude of changes in the various hypothalamic nuclei may be the biological basis for many functional changes in aging, i.e., both endocrine and central alterations, and that only a minority of the possible human hypothalamic changes have so far been studied.
MeSH Terms
- Aging
- Cell Count
- Female
- Gonadotropin-Releasing Hormone
- Humans
- Hypothalamus
- Male
- Neurons
Aging leads to a decrease in circadian organization of behavior. Whether this general observation is related to the finding that in older subjects the arginine-vasopressin (AVP) system in the suprachiasmatic nucleus (SCN) has deteriorated is an unsolved question. Here we assessed circadian organization of running wheel behavior and numbers of AVP cells in the SCN of old voles (n=12, 11. 5 months of age) and compared the results with data from young voles (n=16, 4.5 months of age). A third of the young voles, but three-quarter of the old voles lost circadian rhythmicity. Analysis of daily onset to onset periodicity of running wheel activity at the age of 5 and 10 months in individual voles revealed a significant loss of precision of circadian rhythmicity at the higher age. The number of AVP cells in the SCN of old voles decreased substantially, over 78% compared to young voles in general. AVP cell numbers, however, cannot be directly correlated with the state of rhythmicity in old voles; in one of the three circadian rhythmic old voles the SCN contained the least AVP cells. This study does not support the idea of a causal relationship between aging induced reduction in AVP cells in the SCN and the presence of circadian rhythmicity in behavior.
MeSH Terms
- Aging
- Animals
- Arvicolinae
- Cell Count
- Circadian Rhythm
- Immunohistochemistry
- Male
- Running
- Suprachiasmatic Nucleus
- Vasopressins
The suprachiasmatic nucleus (SCN) is the major circadian pacemaker in mammals. When fetal tissue containing the SCN is transplanted into young rats whose circadian rhythms have been abolished by SCN lesions, the rhythms gradually reappear. Circadian rhythms in many rats deteriorate or disappear with age. The rationale of the present study was that old rats with poor circadian rhythms resemble young rats with SCN lesions. If there is a similar mechanism underlying this resemblance, then fetal tissue containing the SCN should restore rhythms in old rats. Therefore, we implanted such tissue into the third ventricle of intact aged rats with poor circadian rhythms. Body temperature, locomotor activity, and/or drinking were measured simultaneously within subjects. Grafts and hosts were stained immunocytochemically for vasoactive intestinal polypeptide (VIP), arginine vasopressin (AVP), and neuropeptide Y (NPY). Of 23 SCN grafts, 14 were viable (cells observable with Nissl or peptide staining). In 7 of the 14 aged hosts, up to three circadian rhythms were improved or restored. VIP cells were always observable, which was not the case for AVP cells or NPY fibers. In the other seven hosts, no circadian rhythm was improved. Compared with the successful grafts, these unsuccessful grafts had similar amounts of AVP and NPY staining but significantly less VIP cell and/or fiber staining. Fetal cerebellar grafts, which do not contain any of the three peptides, did not improve or restore any rhythms. Thus the degeneration of circadian rhythms in aged rats may be due, at least in part, to deterioration of the aged SCN and in particular, to a loss of function of VIP-containing neurons.
MeSH Terms
- Activity Cycles
- Aging
- Animals
- Body Temperature
- Brain
- Circadian Rhythm
- Drinking
- Female
- Fetal Tissue Transplantation
- Male
- Pituitary Neoplasms
- Rats
- Rats, Long-Evans
- Suprachiasmatic Nucleus
This article deals with the question whether metabolic activity of neurons interferes with their survival during brain aging and Alzheimer's disease (AD). This 'use it or lose it' concept assumes that active neurons have a better chance to survive these conditions. We have monitored activity changes in human hypothalamic nuclei, that show differential survival patterns in aging and AD. The size of the Golgi apparatus (GA) was measured in e.g. the nucleus basalis of Meynert (NBM), that is severely affected in AD, and in the vasopressin (AVP) containing neurons of the supraoptic nucleus (SON) that remain very stable and show no cell loss. In the affected NBM, a strong reduction in activity was found in AD, whereas in the stable SON, an increased activity was present in both conditions. These findings agree with the concept that activation is associated with pronounced stability in aging and AD. Another hypothalamic nucleus is the biological clock (SCN), which is very sensitive to light input. It loses about 35% of its AVP cells in old rats. In order to test the hypothesis that extra stimulation prevents degeneration, the SCN in old rats was activated by means of an increased light input. This could indeed prevent the age-related loss of AVP-neurons in the SCN in low light conditions. Increased light also restored the age-related decreased amplitude in the sleep-wake rhythm. Furthermore, in AD patients, increased amounts of environmental light improved day-night rhythms and reduced behavioural disturbances. These observations are in line with the 'use it or lose it' concept. Furthermore, oxidative damage to the DNA was studied as a) it may accumulate during neuronal aging, and b) activated cells repair their DNA more efficiently. Whereas biochemical measurements of 8OHDG levels were not different in aging or AD, in situ end labeling, that detects fragmented DNA histologically, showed many positive neurons and glial cells in the AD, but not control, hippocampus, whereas in SON and PVN, hardly any damage was detected, which agrees with the 'use it or lose it' concept. Supported by related literature, we conclude that activation may be effective for neuronal maintenance during aging and in AD, and may provide a fruitful basis in the search for future treatment strategies in AD.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Animals
- Biological Clocks
- Cellular Senescence
- DNA Damage
- DNA Repair
- Humans
- Hypothalamus
- Neurons
- Phototherapy
- Rats
In the present report, the peptides arginine vasopressin (AVP), oxytocin (OXT) or their respective antagonists were infused bilaterally into the olfactory bulb to assess their effects upon recognition responses. Recognition responses were determined in a social discrimination paradigm and consisted of measuring the amount of investigation directed to either the same (previously exposed) or novel juvenile rats under conditions in which clear recognition responses are either present as tested with a 30 min inter-exposure interval or absent as tested with a 120 min inter-exposure interval. Infusion of AVP or OXT resulted in preserved recognition responses, as tested with a 120 min inter-exposure interval, compared with that observed in vehicle-infused controls. When animals were infused with the AVP or OXT antagonists using two different doses and tested for the display of recognition as tested with the 30 min inter-exposure interval, no effects of these antagonists were obtained with either dose. These results demonstrate that the olfactory bulb represents an additional important central nervous system target site where these peptides can act to preserve social recognition responses. Moreover, our results suggest that the underlying mechanisms by which peptides function within the olfactory bulb differ as a function of whether they are involved with the display versus preservation of recognition responses.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Discrimination Learning
- Male
- Memory
- Olfactory Bulb
- Oxytocin
- Rats
- Social Behavior
Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to regulate a number of rhythmic processes may be compromised by the time females reach middle age. Therefore, we examined the effects of aging on the rhythmic expression of two neuropeptides synthesized in the SCN, vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization. Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related changes in rhythmicity are associated with alterations in the patterns of expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr rhythm in young females, but by the time animals were middle-aged, this rhythm was gone. The attenuation of rhythmicity was associated with a decline in the level of mRNA per cell and in the number of cells in the SCN producing detectable VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However, in contrast to VIP, the AVP rhythm was not altered in the aging animals. The amount of mRNA per cell and the number of cells expressing AVP mRNA also was not affected with age. Based on these results we conclude that (1) various components of the SCN are differentially affected by aging; and (2) age-related changes in various rhythms may be attributable to changes in the ability of the SCN to transmit timing information to target sites. This may explain why the deterioration of various rhythmic processes occurs at different rates and at different times during the aging process.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Female
- Gene Expression
- Periodicity
- RNA, Messenger
- Rats
- Sex Characteristics
- Suprachiasmatic Nucleus
- Vasoactive Intestinal Peptide
The kidney provides an important contribution to permit the fetus to successfully transition to an independent existence by production of urine with significantly different osmolality compared with plasma. Although recent work has uncovered many aspects of the maturation and regulation of the renal concentrating and diluting mechanism, understanding of how alterations in the expression of aquaporin (AQP) water channels contribute to the formation of urine in the perinatal period is incomplete. Here, we report that both AQP-2 and -3 are expressed during fetal life as early as embryonic d 18 in ureteric buds of rat kidneys, where each is localized to the apical and basolateral membranes of epithelial cells, respectively. Northern analyses demonstrate that the 1.9-kb AQP-2 transcript is present in fetal and postnatal rat kidneys similar to that observed in adults. AQP-2 mRNA expression increases after d 3 of postnatal life. Immunoblotting reveals an increase in total kidney AQP-2 protein particularly with respect to its glycosylated form after postnatal d 3. AQP-3 protein also exhibits a similar alteration likely due to a similar increase in its glycosylation state. Both AQP-2 and AQP-3 display a distribution in the collecting ducts of human postnatal infants and adults identical to that exhibited in rat kidneys. These data show that both AQP-2 and -3 are present in collecting duct epithelia of fetal and postnatal kidneys. Thus, the reduced AVP-responsiveness and decreased urinary concentrating ability of the kidney during the fetal and immediate postnatal period does not appear to be caused by lack of AQP-2 or AQP-3 proteins.
MeSH Terms
- Aging
- Amino Acid Sequence
- Animals
- Animals, Newborn
- Antibodies
- Aquaporin 2
- Aquaporin 3
- Aquaporin 6
- Aquaporins
- Embryonic and Fetal Development
- Epitopes
- Female
- Gene Expression Regulation, Developmental
- Humans
- Infant, Newborn
- Ion Channels
- Kidney
- Male
- Molecular Sequence Data
- Rats
- Rats, Sprague-Dawley
- Ureter
It is well known that urine-concentrating ability decreases with aging and that this decreasing ability results from a reduced sensitivity of the renal collecting duct to arginine vasopressin (AVP). AVP regulates the water channel (aquaporin-2:AQP2) through V2 receptors and increases the water permeability of the collecting duct. To elucidate the mechanism of change with aging in urine-concentrating ability, we investigated the change of V2 receptor and AQP2 mRNA expression in young (8-week-old) and older (7-month-old) rats after dehydration for 2 days. After dehydration, plasma AVP levels in older rats were higher than young rats, and urinary osmolality in older rats was lower than young rats. By Northern blot analysis, there was no significant difference between young and older rats in both V2 receptor and AQP2 mRNA expression before dehydration. After dehydration, V2 receptor mRNA expression in young and older rats decreased in the same degree, suggesting the downregulation of V2 receptors may occur in the mRNA level. Northern blot analysis and in situ hybridization histochemistry showed that AQP2 mRNA expression increased and the increased expression in older rats was less than in young rats. The present study suggests the reduced response of AQP2 mRNA expression to dehydration, observed in 7-month-old rats, might be partially responsible for the decreasing urine-concentrating ability with aging.
MeSH Terms
- Aging
- Animals
- Aquaporin 2
- Aquaporin 6
- Aquaporins
- Dehydration
- Gene Expression Regulation
- Ion Channels
- Rats
The paraventricular (PVN) and supraoptic nucleus (SON) demonstrate a striking stability with respect to cell numbers during aging and Alzheimer's disease (AD). Vasopressin (AVP) neurons even become activated during aging as judged from several parameters for neuronal activity, such as increased AVP plasma levels, enlarged nucleolar as well as cell size and an increased size of the Golgi apparatus in AVP-neurons. The activation possibly occurs as compensation for an age-related loss of AVP-receptors in the kidney. As a specific marker for AVP synthesis, we used quantitative in situ hybridization and estimated total amounts of AVP-mRNA in the entire SON and PVN of 14 control subjects and 14 AD patients that were matched for age, fixation time, postmortem delay and storage time of the tissue in paraffin. Following quantification, no differences were observed in total amounts of AVP-mRNA in the SON or PVN between young and old controls or between young and old AD patients, nor between the entire group of controls and AD patients. A significant negative correlation was found between the volume of the AVP-mRNA signal in the AD SON and age while the total amount of mRNA remained the same. This suggests a redistribution of cells or cell compartments in aging. A significant positive relation in both SON and PVN of AD patients was found between storage time of the paraffin-embedded tissue and the total amount of AVP-mRNA. A significant positive relation was present in the PVN, but not SON between pH of the cerebrospinal fluid, which is a marker for agonal state and the total amount of AVP mRNA. The present unchanged AVP-mRNA levels in SON and PVN confirm earlier observations on the stability of cell numbers in these nuclei in aging and AD. Although on the basis of other parameters, AVP-mRNA upregulation was expected, gradual, chronic stimulation over prolonged periods of time may, possibly, induce alternative mechanisms of regulation such as changes in translatability or in mRNA stability.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Female
- Humans
- In Situ Hybridization
- Male
- Middle Aged
- Paraventricular Hypothalamic Nucleus
- RNA, Messenger
- Regression Analysis
- Supraoptic Nucleus
- Vasopressins
We recently reported that fetal sheep corticotrophs (ACTH-producing cells) at 108 /- 5 d (days) of gestation are relatively more responsive to CRH than to AVP, whereas those at 139 /- 0 d (term = 145 d) and in the adult are more responsive to AVP. To further characterize these developmental changes, we used immunocytochemical, RIA, and cell immunoblotting techniques to examine populations of corticotrophs and individual cells. Immunocytochemical studies revealed that corticotroph frequency decreased from 22 /- 1% of all pituitary cells at 100 d of gestation to 14 /- 1% at 135 d and 9 /- 0% in the adult. RIA measurements of ACTH secretion by cell populations showed that the response of corticotrophs to CRH diminished, whereas that to AVP increased during gestation and into adulthood. Cell blot analysis of individual corticotrophs identified two types of secretory responses (increases in the number of secreting cells and average amount of ACTH released per cell) to CRH or AVP that changed during fetal development. At 100 d of gestation, CRH increased the proportion of secreting cells from 65 /- 3% (no test agent) to approximately 90%; AVP exerted a negligible effect on the relative abundance of secreting cells. At 120 d of gestation, both secretagogues, alone or in combination, increased the proportion of secreting corticotrophs from 49 /- 6% to about 85%. At 135 d of gestation and in the adult, AVP, alone or in combination with CRH, increased secreting corticotrophs from about 53 /- 6% to about 80%. CRH alone exerted a nominal effect on the proportion of secreting cells. Additional analyses showed that, at 100 or 120 d of gestation, the average amount of ACTH secreted by individual corticotrophs did not change in response to CRH or AVP. However, near term and into adulthood, the average quantity of ACTH released from individual cells increased in response to these agents. Our findings suggest that maturational changes in fetal corticotrophs dictate whether their secretory response to CRH or AVP results from an increase in the proportion of cells secreting ACTH and (or) an increase in the average amount of hormone secreted by individual cells.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Embryonic and Fetal Development
- Female
- Fetus
- Immunoblotting
- Immunohistochemistry
- Pituitary Gland, Anterior
- Pregnancy
- Sheep
Monogamous prairie voles (Microtus ochrogaster) and promiscuous montane voles (Microtus montanus) exhibit remarkable differences in the distribution of vasopressin (AVP) receptors in the adult brain. This difference in receptor distribution is associated with species differences in the behaviors, including pair bond formation and paternal care, found selectively in the monogamous vole. To investigate a potential mechanism for this species difference in AVP receptors, the present study examined the ontogeny of receptor binding in the two species to determine whether the adult maps arose from a shared pattern in development. By using 125I-linear-AVP, which is a selective high-affinity ligand for the V1a receptor, we found early appearance and transient expression of AVP receptor binding during postnatal development in both species. However, the ontogenetic patterns of regional AVP receptor binding were species specific. In the diagonal band, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, prairie voles had higher AVP receptor binding at birth than montane voles, and this difference persisted with little variation into adulthood. In these areas, therefore, species differences in AVP receptor binding appeared to be determined primarily by genetic or prenatal factors. In the lateral septum, both species had low levels of AVP receptor binding at birth. Thereafter, the binding increased rapidly in montane voles, but it remained unchanged in prairie voles. In the cingulate cortex, AVP receptor binding in prairie voles showed a peak in early development with a subsequent decline and reached the adult level at weaning, whereas the binding in montane voles remained unchanged into adulthood. A similar but opposite pattern was found in the frontoparietal cortex, in which AVP receptor binding showed an early peak in montane voles but did not change significantly in prairie voles. These results demonstrate that 1) species differences in regional AVP receptor binding are evident in the early postnatal period and, in several areas, may be determined by genetic or prenatal factors, and 2) AVP may target brain areas differently in infant and adult prairie and montane voles and, thus, could exert differential effects on the organization of the central nervous system in the two species of voles.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arvicolinae
- Autoradiography
- Brain
- Receptors, Vasopressin
- Sexual Behavior, Animal
- Species Specificity
Physiological changes in the pituitary gland with age have not been fully evaluated. The aim of this study was to clarify the morphological characteristics of the pituitary gland by magnetic resonance imaging(MRI) in elderly subjects and to relate them to pituitary hormone secretion. We investigated the pituitary MRI in 59 elderly (15 males, 44 females; median 82 years) and 41 young (13 males, 28 females; median 34 years) healthy subjects. Pituitary height, width and volume in the elderly subjects were less than those in the young subjects. Empty sella was more frequently observed in the elderly subjects (19%), especially women, than in the young ones. However, no relation was observed between the pituitary size or volume and basal levels of anterior pituitary hormones. Posterior pituitary bright signal(PBS) on T1-weighted MRI, which is thought to reflect its storage of the neurophysin-peptide complex, was not detected in 29% of the elderly subjects while it could be detected in all the young subjects. None of the elderly subjects showed clinical signs or symptoms of diabetes insipidus. Fasting plasma osmolarity and AVP in the elderly subjects were significantly higher than in the young subjects. Moreover, plasma AVP was significantly higher in the elderly subjects without the PBS than in those with the PBS. It is suggested that the excessive release of AVP from the posterior pituitary as a result of persistently raised plasma osmolality in the elderly subjects may lead to depletion of the neurosecretory granules in the posterior pituitary gland and may result in disappearance of the posterior pituitary bright signal on T1-weighted MRI. As these morphological changes might relate to the normal physiological occurrence of ageing, we should be cautious in evaluating MRI of the pituitary gland in elderly subjects.
MeSH Terms
- Adrenocorticotropic Hormone
- Adult
- Aged
- Aged, 80 and over
- Aging
- Arginine Vasopressin
- Female
- Follicle Stimulating Hormone
- Humans
- Hydrocortisone
- Luteinizing Hormone
- Magnetic Resonance Imaging
- Male
- Osmolar Concentration
- Pituitary Gland
- Pituitary Hormones
- Thyroid Hormones
Immunohistochemistry and morphometry were used to study the age-related changes in the vasopressin (AVP) and oxytocin (OXT) nerve cells in the paraventricular (PVN), supraoptic (SON) and suprachiasmatic (SCN) nuclei of 3-, 11- and 28-month-old rats. The results showed a statistically significant reduction in the mean number of AVP cells in the PVN, SON and SCN, and of OXT cells in the PVN with advancing age. Different age-related changes in the mean size of the immunoreactive cells were found in the three nuclei: a significant and transitory increase in the AVP and OXT cell sizes in the PVN, a tendency towards increasing the AVP and OXT cell sizes in the SON, and a significant and gradual decrease in the AVP cell size in the SCN. The combination of the morphometric data and staining patterns of the AVP and OXT perikarya and fibers in the PVN and SON pointed to an increased transport of AVP and OXT in 11-month-old rats as well as to a decreased production of these peptides in the PVN of 28-month-old rats. Taken together the staining pattern and the morphometric results showed a progressive loss of AVP cells in the SCN in aging.
MeSH Terms
- Aging
- Animals
- Cell Size
- Histocytochemistry
- Hypothalamus
- Immunohistochemistry
- Male
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Rats
- Rats, Wistar
- Suprachiasmatic Nucleus
- Supraoptic Nucleus
- Vasopressins
Because cardiomyopathic hamsters (CMHs) in the lesion-forming period of their disease are more susceptible to the lethal effects of stress than older CMHs, we tested the hypothesis that different pathophysiological effects of stress may occur: coronary vasospasm in younger CMHs and congestive heart failure in older ones. CMHs aged 2.5 and 6.5 months were stressed with 2 h supine cold immobilization for 5 consecutive days. Three, 5 and 7 days after stress, the hearts were excised and perfused using a modified Langendorff system. Maximum /- dP/dt, developed pressure, ventricular relaxation time (Tau) and coronary vascular resistance (CVR) were recorded and CVR was also measured following coronary infusion of arginine vasopressin (AVP). Stress produced ventricular dysfunction (decreased maximum /- dP/dt, developed pressure, and increased Tau) in older CMHs (P < 0.05) but not in younger CMHs. Baseline CVR in younger CMHs was significantly higher than in older CMHs (P < 0.01) and AVP infusion produced a bigger increase in CVR in younger stressed CMHs than in either younger nonstressed or older stressed CMHs (P < 0.05). The younger CMH heart exhibits greater resting vascular tone and stress produces coronary vasoconstriction that is consistent with coronary spasm. In contrast, the older CMH experiences a decrease in cardiac function which remains 7 days after stress and indicates an exacerbation of CHF from the mild form existing prior to stress. The lethal effects of stress may occur because of the activation of different pathological processes in younger and older CMHs.
MeSH Terms
- Age Factors
- Aging
- Animals
- Arginine Vasopressin
- Cardiomyopathies
- Coronary Vasospasm
- Coronary Vessels
- Cricetinae
- Heart
- Heart Failure
- Stress, Psychological
- Vascular Resistance
Synthetic ovine corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP) were injected alone or in combination (for each peptide 1 microgram/kg body weight) in 7-day-old and adult rats and rabbits. Fifteen minutes after the interscapulary injection, blood was collected for plasma adrenocorticotrophin (ACTH), corticosterone and aldosterone evaluation by RIA. The different circulating forms of ACTH were isolated by Sephadex G50 column chromatography with 1% formic acid and measured by RIA using 1-24 ACTH as standard. Such experiments were previously described in lambs and guinea-pigs using the same schedule. In young and adult rabbits the predominant circulating IR-ACTH form was 'big' ACTH; after stimulation with CRF, AVP or CRF AVP the 'intermediate' IR-ACTH was greatly increased in adults, but no change was observed in young rabbits. In young and adult rats the predominant circulating form was "intermediate' ACTH in control and injected animals; ACTH increased after CRF alone or in combination with AVP, but not after AVP alone. In both species the 'intermediate' forms of IR-ACTH were not eluted at the same time by chromatography, and calculated molecular weights were different: 14500 in rats and 9500 in rabbits. Plasma corticosterone and aldosterone were increased in rat and rabbit adults after CRF and AVP; however, they remained unchanged in young rabbits and slightly increased only after CRF in young rats in which corticosterone remained at a very low concentration compared with that in adults. Hence, the pituitary-adrenal axis of 7-day-old rabbits and rats in less reactive than that of sheep and guinea-pig of the same age.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Aldosterone
- Animals
- Arginine Vasopressin
- Corticosterone
- Corticotropin-Releasing Hormone
- Male
- Rabbits
- Rats
- Rats, Wistar
- Species Specificity
Most magnocellular hypothalamic neurons synthesize the precursor for either vasopressin (AVP) or oxytocin (OT). The AVP precursor is cleaved to give AVP, AVP-associated neurophysin (AVP-NP) and a glycopeptide (GP), whereas the OT precursor gives OT and OT-NP. In Brattleboro rats a frame-shift mutation in the AVP-NP-encoding region of the gene prevents the secretion of AVP by the cells and, in most AVP neurons, AVP itself is virtually undetectable. A small number of magnocellular neurons in homozygous Brattleboro rats contain very large accumulations of peptide in distended saccules of rough endoplasmic reticulum (RER), and this peptide is immunoreactive for AVP and C-terminal OT-NP, but not for OT, AVP-NP or GP (Pow et al., 1992). We have now shown that this results from somatic non-homologous crossing over of the AVP and OT genes, resulting in the production of hybrid mRNA molecules with the 5'end of the AVP sequence and the 3' end of the OT sequence (AVP/OT transcripts). In most cases, the crossing over occurs within the highly homologous B exons (Mohr et al., 1994). In addition to the production of AVP/OT hybrid transcripts, polymerase chain reaction (PCR) amplification of mRNA from the hypothalami of homozygous rats also reveals OT/AVP hybrid transcripts, with 5' OT sequences and 3' AVP sequences. Furthermore, both types of hybrid transcript are not restricted to homozygous Brattleboro rats but can also be found in normal Long Evans animals. To date, we have not been able to locate cells in which the OT/AVP hybrids are produced; all the magnocellular neurons with hybrid peptide accumulations in the RER so far studied have been shown by immunocytochemistry to be of the AVP/OT type. In both normal and homozygous Brattleboro rats large accumulations of peptide do occur in the RER of OT-producing neurons but the peptide is immunoreactive for OT and OT-NP but not for AVP, AVP-NP or GP. Such cells increase in number 10-fold after injection of 20 micrograms estradiol daily for 7 days (Pow et al., 1991). Why this apparently normal gene product accumulates within the RER remains to be determined.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Crossing Over, Genetic
- Endoplasmic Reticulum, Rough
- Hypothalamus
- Mutation
- Neurons
- Oxytocin
- Protein Precursors
- Rats
- Rats, Brattleboro
To understand the regulation of vasopressin receptors in an animal model of hypertension, localization and age-related changes in renal arginine vasopressin (AVP) receptors in spontaneously hypertensive rats (SHR) were investigated using in vitro (macro) autoradiography and a radiolabeled receptor assay. Autoradiography localized renal AVP V2 receptors to the distal tubules and collecting ducts in the medulla. We also found small numbers of AVP-binding sites within glomeruli, possibly representing V1 receptors in the mesangium. The radiolabeled receptor assay of the medulla membrane fraction revealed that the binding affinity of renal V2 receptors did not differ significantly between SHR and control Wistar-Kyoto rats in any age group. However, the binding capacity (Bmax) for V2 receptors in 12-week-old SHR was significantly increased (p < 0.025) as compared with that of age-matched control rats. The Bmax values for V2 receptors in 3- and 7-week-old SHR were not significantly different from those of age-matched controls. There was no significant change in urine volume between SHR and control rats at the age of 12 weeks. The mean plasma AVP concentration in SHR increased at 7 and 12 weeks of age. These findings suggest that SHR have different developmental changes in kidney AVP receptors and that renal V2 receptors play a role in maintaining fluid homeostasis in SHR with established hypertension.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Autoradiography
- Blood Pressure
- Glomerular Mesangium
- Hypertension
- Kidney Tubules, Collecting
- Kidney Tubules, Distal
- Male
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Rats, Wistar
- Receptors, Vasopressin
We investigated whether increased light input can counteract the age-related decrease in vasopressin- (AVP) and vasoactive intestinal polypeptide (VIP)-expressing neurons of the suprachiasmatic nucleus (SCN) by determining the numbers of these neurons in rats of different ages, housed under low or high intensities of light. The significant age-related decrease for AVP was prevented in old animals after high light housing. For VIP, no effects were found.
MeSH Terms
- Aging
- Animals
- Cell Count
- Immunohistochemistry
- Light
- Male
- Neuronal Plasticity
- Neurons
- Rats
- Rats, Inbred BN
- Suprachiasmatic Nucleus
- Vasopressins
Fischer 344 (F344) rats display focal and diffuse glomerulosclerosis with aging postulated to result from loss of normal mesangial cell intrinsic function, e.g., vasoactive hormone signaling, or preservation of normal responsiveness to extrinsic growth factors. In 3-, 17-, and 24-month-old F344 male rats, glomerular structure, measured by PC-based morphometry, and function were compared. Immunoperoxidase staining of glomerular proliferating cell nuclear antigen (PCNA) detected cellular proliferation. Primary cultured mesangial cells from the 3 age groups were studied in parallel. Calcium (Ca2 ) signaling, measured by Fura-2 fluorescence, contraction to vasopressin (AVP) 1 microM, measured by videomicroscopy, and proliferative response to platelet-derived growth factor-beta beta (PDGF) were compared. Proteinuria was 13 /- 4, 38 /- 17, and 110 /- 35 mg/24 hours at 3, 17, and 24 months, respectively (n = 5, mean /- SE, p < .01, 3 vs 24 months), with no change in 24-hour creatinine clearances. Glomerular volumes (n = 200/group) for 3, 17, and 24 months, respectively, were .30 /- .01, .60 /- .02, .74 /- 0.2 x 10(6) micron3 (p < .001, 3 months vs 17 months, and 17 vs 24 months). Glomerular basement membrane (GBM) widths and fractional mesangial volumes increased significantly with aging. Glomerular cell PCNA staining remained positive at 24 months. Cultured mesangial cell Ca2 signaling and contraction to AVP were unchanged with aging. Proliferation to PDGF, which was partially inhibited with verapamil, was similar at 3 and 24 months. In the Fischer 344 rat, mesangial cell Ca2 signaling, contraction, and proliferation responsiveness are unchanged with aging. Continued growth is associated with the glomerulosclerosis of aging.
MeSH Terms
- Aging
- Animals
- Basement Membrane
- Cell Communication
- Cell Division
- Cells, Cultured
- Glomerular Mesangium
- Glomerulosclerosis, Focal Segmental
- Kidney Glomerulus
- Male
- Platelet-Derived Growth Factor
- Proliferating Cell Nuclear Antigen
- Rats
- Rats, Inbred F344
- Specific Pathogen-Free Organisms
- Vasopressins
To assess the effects of aging on hypothalamic-pituitary-adrenal (HPA) axis responsivity, we compared the plasma cortisol and adrenocorticotropin (ACTH) responses to hypertonic saline infusion between normal older and young human volunteers. We administered a 90 min hypertonic saline infusion (5% sodium chloride at 0.06 ml/kg/min) and a 90 min placebo infusion (0.9% sodium chloride at 0.06 ml/kg/min) to normal young subjects (n = 13, age = 29 /- 2 years) and normal older subjects (n = 8, age = 63 /- 3 years). Plasma cortisol, ACTH, osmolality and arginine vasopressin (AVP) were measured before and at 30 min intervals during the infusions. The rate of increase in plasma osmolality and AVP induced by hypertonic saline infusion was similar between groups. The plasma cortisol increase during hypertonic saline infusion was greater in normal older subjects than in young subjects (p = .03), but a stimulatory effect of hypertonic saline infusion on plasma ACTH was not apparent in either older or young subjects. These results suggest increased sensitivity with human aging to stimulation of cortisol release by hypertonic saline infusion at the adrenocortical level of the HPA axis.
MeSH Terms
- Adrenocorticotropic Hormone
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Female
- Humans
- Hydrocortisone
- Hypothalamo-Hypophyseal System
- Male
- Middle Aged
- Pituitary-Adrenal System
- Reference Values
- Saline Solution, Hypertonic
- Single-Blind Method
- Water-Electrolyte Balance
Inhibition of dehydration-induced arginine vasopressin (AVP) secretion and thirst depends on removal of osmotic and hemodynamic stimuli as well as on preabsorptive oropharyngeal factors that reduce thirst and AVP secretion on drinking before correction of the water deficits. Plasma atrial natriuretic peptide (ANP) levels may also change with drinking. Therefore, the thirst and plasma responses to oral water loads (10 ml/kg) in 10 healthy old (64-76 yr) and young (20-32 yr) 24-h water-deprived men were investigated. After 24-h water deprivation plasma sodium, osmolality, and AVP were increased similarly in both groups (P < 0.001). Plasma ANP levels fell after dehydration similarly in both groups (P < 0.05) but were always higher in the older group (P < 0.05). However, although thirst increased in both groups (P < 0.05), this was significantly less in the elderly (P < 0.05). After the water load, thirst was reduced in both groups throughout the study (P < 0.05). However, plasma AVP fell immediately after drinking only in the young group and rose to postdeprivation levels after 15 min. Plasma AVP was not different from postdeprivation throughout in the old group and after 15 min in the young group presumably because the water load was insufficient to replace their water deficits. In the young group only, plasma ANP rose to 182 /- 43% of postdeprivation levels at 3 min after drinking (P < 0.05). These results demonstrate reduced oropharyngeal inhibition of AVP secretion after drinking in healthy elderly men but maintained inhibition of thirst.
MeSH Terms
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Atrial Natriuretic Factor
- Dehydration
- Drinking
- Humans
- Male
- Middle Aged
- Osmolar Concentration
- Sodium
- Thirst
Disturbances in homoeostatic capacity are typical of the ageing process. Changes in the neuroendocrine controls of salt and water homoeostasis with age make elderly people more susceptible to fluid and electrolyte disturbances such as dehydration and overhydration. Not only do elderly subjects show reduced thirst and water intake following dehydration, but their kidneys are less able to retain water. This reduced thirst and water intake is not dependent on palatability of the liquids offered as the amounts drunk are no different if water alone or a variety of beverages are offered to healthy elderly dehydrated men. It is of interest that the arginine vasopressin (AVP) response to dehydration is maintained in elderly subjects, indicating that their reduced renal water retentive capacity is due to relative renal resistance to vasopressin. The mechanism underlying the reduced thirst is unclear. Dehydration causes plasma hypertonicity and reduced extracellular fluid (ECF) volume, both of which stimulate thirst and AVP secretion. Elderly subjects show deficits in sensing the reduced ECF volume through reduced low and high pressure baroreceptor sensitivity. In contrast, while the AVP responses to hypertonicity are maintained, the thirst responses seem to be reduced. It seems unlikely that the primary sensing 'osmoreceptor' neurons in the hypothalamus leading to AVP secretion or thirst would be differentially affected by age. Therefore the thirst deficit may result from changes with age in the more poorly defined pathways that bring thirst to consciousness. Following rehydration, thirst and AVP secretion are inhibited in young individuals thus avoiding overhydration.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aged
- Aging
- Animals
- Arginine Vasopressin
- Dehydration
- Homeostasis
- Humans
- Neurosecretory Systems
- Rats
- Thirst
- Water-Electrolyte Balance
1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR) stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5-7 weeks and 7-9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Blood Pressure
- Ganglia, Sympathetic
- Hypertension
- Male
- Pentolinium Tartrate
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Rats, Sprague-Dawley
- Rats, Wistar
We investigated the association of age with supine and ambulant plasma osmolality (pOSM) and arginine vasopressin (AVP). Twenty-eight healthy-status-defined subjects were studied. Following an overnight fast, blood samples were withdrawn after one hour supine rest and two hours' ambulation. Neither supine nor ambulant pOSM nor AVP varied significantly with age. The results suggest that in healthy subjects age does not influence plasma osmolality or AVP.
MeSH Terms
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Female
- Humans
- Male
- Middle Aged
- Reference Values
- Water-Electrolyte Balance
The heart of the young Syrian cardiomyopathic hamster (CMH) displays discrete patches of active myocytolytic necrosis and it has been hypothesised that these lesions are triggered by arteriolar spasm. Accordingly, we tested the theory that the coronary vasoconstrictor response to arginine vasopressin (AVP) infusion is more vigorous in the actively necrotising young (2-3 month old) CMH than in age matched normal hamsters, 5-6 month old CMHs in the histologically quiescent phase of the disease, or 5-6 month old normal hamsters. An isovolumetric isolated heart preparation was used in which the coronary arteries were perfused with Krebs-Henseleit buffer at constant flow by a syringe pump. Coronary vascular resistance was determined by the ratio of measured perfusion pressure to flow rate during extended diastoles. There were no significant differences in baseline coronary vascular resistance among the four groups. The increase in resistance with AVP infusion (0.54 pressor units.min-1) was significantly greater (p < 0.01) in the young CMH [6.66(SEM 4.75) mm Hg.ml-1.min-1] than in the old CMH [1.66(0.78)], the young normal [1.10(1.07)], and the old normal [2.72(1.86)] groups. There is increased vasoconstrictive responsiveness in the young CMH coronary vasculature. The results suggest a broader coronary abnormality in this myopathic model and are consistent with the microvascular spasm hypothesis of myocytolytic lesion formation.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Coronary Vessels
- Cricetinae
- Heart Failure
- Male
- Mesocricetus
- Microcirculation
- Perfusion
- Vascular Resistance
- Vasoconstriction
The supraoptic (SON) and paraventricular nucleus (PVN) of the human hypothalamus produce vasopressin (AVP) and oxytocin (OXT). Since in these nuclei no cells are lost during aging or Alzheimer's Disease (AD), factors are searched for which may be responsible for this remarkable stability. Earlier work in both rat and human indicated that the peptide synthesis of these neurons was activated in the oldest age groups as judged from increased neuronal and nuclear size and AVP plasma levels. The size of the Golgi Apparatus (GA) has proved to be a very sensitive parameter for the synthetic activity of these neurosecretory cells in animal experiments. In order to determine changes in the GA during aging and in Alzheimer's Disease, we applied a polyclonal antiserum against immunoaffinity purified MG-160, a sialoglycoprotein of the medial cisternae of the GA, on formalin-fixed and paraffin-embedded sections of the SON and PVN of patients ranging in age from 29 to 97 years. However, our standard fixation procedure masked antigenic sites resulting in a minimal immunocytochemical staining in most of the tissues examined. It appeared to be possible, however, to retrieve the antigen and to obtain an excellent staining of the GA by heating sections in a microwave oven before immunostaining. Following this procedure, an increase in size and intensity of the GA became apparent in individuals from about 70 years and older. In AD patients a similar increase in size and intensity of the immunostained GA was observed. Taken together, these results indicate that SON and PVN neurons are activated during the course of aging and also in AD and that this activation takes place at an earlier age than observed previously by other cellular parameters.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Female
- Golgi Apparatus
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Neurons
- Paraventricular Hypothalamic Nucleus
- Receptors, Cell Surface
- Receptors, Fibroblast Growth Factor
- Sialoglycoproteins
- Supraoptic Nucleus
To evaluate the influence of age on plasma arginine vasopressin (AVP) concentrations and the relationship between plasma AVP and serum osmolality in younger and older subjects, and in the elderly, to assess the effect of gender on plasma AVP concentration and to determine the impact of prostaglandin blockade on renal responsiveness to AVP. Cross-sectional study; randomized, double-blind, crossover, placebo-controlled study. The Renal Laboratory, Royal North Shore Hospital (younger adults) and Clinical Room, St Vincents Hospital (elderly subjects). 45 younger adults (35 /- 9 years), and 41 elderly subjects (29 males, 12 females; 78 /- 3 years). All subjects were healthy and non-institutionalized. The elderly subjects were screened to exclude significant pathology (clinical assessment, multiple investigations). Blood samples were drawn from all younger and elderly subjects. The elderly subjects were randomly allocated indomethacin or placebo for 1 month. Following a 1 to 2-week washout, the alternative was administered for a further 1 month. Plasma AVP and serum osmolality and plasma AVP, serum, and urine osmolality at baseline were measured on indomethacin and placebo. In the elderly subjects, baseline plasma AVP concentration was significantly higher than in the younger subjects studied (4.7 /- 0.7 vs 2.1 /- 0.2 pg/mL respectively; P = 0.0003). Plasma AVP was strongly correlated with serum osmolality in the younger subjects (r = 0.76, P = 0.0001) but not in the elderly cohort (r = -0.18, P = 0.26). No difference was found between the sexes in plasma AVP (P = 0.89), and indomethacin treatment did not alter the plasma AVP/urine osmolality ratio (P = 0.85) in the elderly subjects. In addition, changes in plasma AVP with indomethacin therapy did not correlate with changes in serum osmolality (r = 0.16, P = 0.09). Aging is accompanied by an increase in plasma AVP concentrations. In healthy, elderly subjects, plasma AVP is not dependent on serum osmolality and is not influenced by gender. Indomethacin has no effect on the renal responsiveness to plasma AVP.
MeSH Terms
- Adult
- Age Factors
- Aged
- Aging
- Arginine Vasopressin
- Cross-Sectional Studies
- Double-Blind Method
- Female
- Humans
- Indomethacin
- Kidney
- Male
- Middle Aged
- Osmolar Concentration
- Sex Factors
- Water-Electrolyte Balance
Axon terminals in the posterior pituitary store large quantities of the hormone vasopressin (AVP), buffering the synthesizing neurons in the hypothalamus against acute changes in physiological demand for hormone release. The dynamics of pituitary AVP content reflect the competing processes of release and synthesis. This report demonstrates substantial increases in pituitary AVP content in the maturing rat. Between 7-10 weeks of age, the total pituitary AVP content in the rat increases from 957 /- 72 to 1667 /- 160 ng. Cross-sectional data indicate a parallel relationship between body weight and pituitary AVP content. Nevertheless, weight maintenance does not affect age-related increases in AVP content. Decreasing demand for hormone release and synthesis by inducing hyponatremia blocks subsequent pituitary accumulation. After withdrawing the hyponatremic experimental conditions, animals resume accumulation of pituitary AVP, but do not catch up to age-matched controls. This indicates that increases in pituitary AVP content do not result from a feedback signal from the neural lobe, but rather, pituitary AVP levels passively reflect changes in hormone release and compensatory synthesis.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Cross-Sectional Studies
- Gene Expression Regulation
- Longitudinal Studies
- Male
- Pituitary Gland, Posterior
- Rats
- Rats, Sprague-Dawley
- Sodium
- Vasopressins
Aging is frequently associated with changes in physiological and cognitive processes. Among these changes is a distinct dysregulation of the hypothalamic-pituitary-adrenal axis. In the current experiments, aspects of hypothalamic-pituitary-adrenal axis function were compared in young (3- to 4-month-old) and aged (21- to 24-month-old) Fisher 344/N male rats. Basal ACTH and corticosterone levels during the circadian trough were elevated in aged compared to young rats. During the evening peak of the circadian cycle, plasma ACTH levels in the young and aged rats were comparable; however, aged rats had significantly lower corticosterone levels than young rats. Stimulus-induced secretion of pituitary-adrenal hormones was attenuated in aged rats. The ACTH response to hemorrhage in the aged group was only 45 /- 3% of the hemorrhage response in young rats. Pituitary responsiveness to an iv CRF challenge was 58 /- 6% of that in the young population. These changes were associated with a 38 /- 5% loss of anterior pituitary CRF receptor number in the aged population. Changes in the hypothalamic regulation of pituitary-adrenal function were also evident in the aged rats. Hypophysial-portal blood concentrations of CRF were significantly greater in aged (56 /- 6 pM) compared to young rats (37 /- 4 pM; P < 0.02, by two-tailed unpaired t test; n = 8/group), whereas portal levels of arginine vasopressin were significantly reduced in aged (0.56 /- 0.01 nM) compared to young rats (0.89 /- 0.01 nM; P < 0.01, by two-tailed unpaired t test; mean /- SEM; n = 8/group). Portal CRF responses to hemorrhage were significantly (P < 0.01) greater in aged rats, whereas hemorrhage-stimulated increases in portal AVP levels were significantly (P < 0.01) reduced in the aged group compared to those in the young rats. Finally, regional assay of CRF content demonstrated significant reductions in the median eminence and frontal cortex of aged rats compared to young rats, whereas in situ hybridization analysis failed to reveal age-related differences in paraventricular CRF mRNA levels. Overall, these observations are consonant with the hypothesis that senescence is associated with hypothalamic CRF hypersecretion and a consequent down-regulation of corticotrope CRF receptor.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Corticosterone
- Corticotropin-Releasing Hormone
- Hypothalamo-Hypophyseal System
- Male
- Pituitary-Adrenal System
- RNA, Messenger
- Rats
- Rats, Inbred F344
- Receptors, Corticotropin-Releasing Hormone
Arginine vasopressin (AVP) has been found to participate in blood pressure maintenance especially when other pressor systems are endogenously or pharmacologically impaired. The purpose of this study was to assess the pressor contribution of AVP to orthostatic blood pressure maintenance in otherwise healthy patients with essential hypertension. Twenty-seven patients were grouped according to age (young n = 13, elderly n = 14) and race (white n = 13, black n = 14). Integrity of autonomic nervous system (ANS) was assessed by Valsalva's maneuver, cold pressor test and head-up tilt. AVP contribution to blood pressure was estimated by the fall in mean arterial pressure in response to IV injection of 0.5 mg of a V1 AVP inhibitor (AVPi). Elderly subjects were found to have a mild (subclinical) ANS impairment as indicated by absence of bradycardia in phase 4 of Valsalva's maneuver and hypotension without concurrent tachycardia during head up tilt. Depressor responses to AVPi while subjects were in the upright position, were greater in elderly and blacks (-15 /- 11 mm Hg and -15 /- 12 mm Hg, respectively, P < .05) than young and whites (-8 /- 6 and -7 /- 6 mm Hg, respectively, ns). The greater importance of the AVP component in the elderly may be at least partially explained by a mild ANS impairement, whereas hormonal characteristics of hypertension in blacks may explain greater AVPi induced fall in mean arterial pressure. Our data show that both age and race influence the response to AVPi.
MeSH Terms
- Adult
- African Continental Ancestry Group
- Aged
- Aging
- Arginine Vasopressin
- Autonomic Nervous System
- Blood Pressure
- Cold Temperature
- European Continental Ancestry Group
- Heart Rate
- Humans
- Hypertension
- Middle Aged
- Posture
- Radioimmunoassay
- Valsalva Maneuver
Recent studies on experimental animals showed that long term activation of the hypothalamo-pituitary-adrenal axis is associated with increased vasopressin (AVP) colocalization in paraventricular corticotropin-releasing hormone (CRH) neurons. In the present study we estimated the fraction of CRH neurons in which AVP is colocalized by double label immunocytochemistry in hypothalami of 10 control subjects of 21-91 years of age and 10 age-matched Alzheimer patients. CRH neurons in the paraventricular nucleus (PVN) of Alzheimer patients and control subjects showed similar age dependent increases in AVP colocalization. Based on this parameter, it seems that CRH neurons of Alzheimer patients are not overactivated as compared to age-matched controls, but e.g. changes in m-RNA for CRH should still be established.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Corticotropin-Releasing Hormone
- Humans
- Immunohistochemistry
- Middle Aged
- Neurons
- Paraventricular Hypothalamic Nucleus
- RNA, Messenger
Kidney dysfunction has been observed in aged humans and rats, the primary cause of which may reside in the kidney itself or in the hypothalamus. The latter possibility is suggested by the increased release of AVP in response to salt infusion in humans. The effect of age on the relationship between plasma osmolality and plasma AVP concentration has never been verified in an animal model. Therefore, in the present study, 9% salt solution was infused into adult and aged Lewis rats, and plasma AVP concentration and osmolality were measured. Basal plasma AVP concentration, osmolality and total water intake were not altered in aged Lewis rats as compared with adult animals, indicating the absence of overt disturbances in water homeostasis. Infusion of 9% salt solution resulted in a linear increase in plasma osmolality in both adult and aged rats. Plasma osmolality increased more with time in aged animals than in adult animals, suggesting an age-related difference in kidney function during salt infusion. Plasma AVP concentration increased 50% less with osmolality at relatively low osmolalities, but not at relatively high osmolalities. The altered relationship between plasma osmolality and plasma AVP concentration in rats with age may be related to changes in neurons monitoring osmolality or to changes in baroreflex regulation. The data suggest that reduced kidney function with age does not result from an altered relationship between plasma osmolality and plasma AVP concentration.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Male
- Osmolar Concentration
- Radioimmunoassay
- Rats
- Rats, Inbred Lew
Vasopressin has been shown to improve electrophysiological signs of cognitive stimulus processing in young human subjects. This study compared the effects of arginine vasopressin (AVP) on central nervous stimulus processing in old and young mentally healthy subjects. To assess aspects of cognitive stimulus processing, event-related potentials (ERPs) were recorded. A total of 22 old and 28 young subjects were tested on two subsequent days. Substances were administered intranasally 22, 12, and 1 hour(s) prior to experimental sessions. Prior to the first session, all subjects received placebo. Prior to the second session, 11 of the elderly and 15 of the young subjects received AVP (3 x 10 IU in each nostril) while the remaining subjects again received placebo. The study was held double blind. The subjects performed an auditory "oddball" task consisting of rare target tones (requiring a button press response) interspersed throughout a sequence of frequent standard tones while an electroencephalogram was recorded. Differences between young and aged subjects were more pronounced for ERPs to targets than standard pips. Latencies of the N2 and P3 waves of the ERP to targets were significantly prolonged, and the P3 amplitude was diminished in the elderly subjects (p < .01). N2 amplitude was enhanced in both age groups by vasopressin (p < .05). However, AVP treatment significantly enlarged the N2-P3 difference amplitude only in young subjects. The results indicate that AVP improves ERP signs of stimulus processing associated with attentional mechanisms. However, the ERP signs of age-related cognitive impairment remained unimproved after AVP.
MeSH Terms
- Administration, Intranasal
- Adult
- Aged
- Aged, 80 and over
- Aging
- Analysis of Variance
- Arginine Vasopressin
- Arousal
- Attention
- Cognition
- Double-Blind Method
- Electroencephalography
- Evoked Potentials, Auditory
- Female
- Humans
- Male
- Placebos
- Reaction Time
Arginine vasopressin (AVP) is a peptide hormone which is found in neurons within the paraventricular (PVN) and the supraoptic (SON) nuclei of the hypothalamus. In fetal sheep, this neuropeptide is involved in maturational processes and adaptive responses to 'stress'. This study examined the effect of age on the total number and distribution of AVP-containing neurons in the PVN and SON of fetal sheep and newborn lambs by quantitative light-microscopic immunocytochemistry. Serial coronal sections of hypothalami from three groups of animals were studied: fetuses at 104-109 days of gestation (n = 6) comprising the early group, fetuses at 130-139 days of gestation (n = 5) comprising the late group and newborn lambs at 12-20 postnatal days (n = 5) comprising the neonatal group. This period of development was chosen since adaptive mechanisms to stress are operative at or near the time of birth. Hypothalamic dimensions were measured to determine if maturation had an effect on the size of the AVP-containing subregions of the hypothalamus during this period of development. Dimensions included: ventricle height, optic chiasm width, distances from the dorsal margin of the ventricle to the lateral and medial margins of the optic tract, and distance between the medial margins of the optic tracts. As expected, with increase in maturational age, overall dimensions of the AVP-containing subregions increased significantly (p < 0.05). When early- and late-gestation fetuses were compared to newborn lambs, there was a significant increase in the total number of immunoreactive neurons in both the PVN (p < 0.01, Anova) and SON (p < 0.001, Anova) with age. With advancing age, we also observed an increase in the density of AVP neurons in the middle subregion of the PVN and in the midrostral subregion of the SON. These data suggest that, during the late gestational and early postnatal period, de novo synthesis of AVP genes occurs in these hypothalamic nuclei. This study provides a baseline for further investigation to study the effects of stress on these neurons in the developing ovine fetus and newborn lamb.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Female
- Fetus
- Gestational Age
- Hypothalamus
- Neurons
- Paraventricular Hypothalamic Nucleus
- Pregnancy
- Sheep
- Supraoptic Nucleus
The supraoptic (SON) and paraventricular nuclei (PVN) of the human hypothalamus are production sites of vasopressin (AVP) and oxytocin (OXT). Although the hypothalamus is affected in Alzheimer's disease (AD), previous work has not only shown that in these two nuclei no neurons are lost, neither during aging nor in AD, but that the number of AVP-expressing neurons and their nucleolar size had even increased with age. These observations indicated that the peptide synthesis of the AVP neurons was activated in the oldest age-groups. Recently published, qualitative observations, using the area of the Golgi Apparatus (GA) as a sensitive parameter for neurosecretory activity, confirmed the activation of SON and PVN neurons with age in human; however, in this report the neurons were not identified according to their neuropeptide content. In the present quantitative study we determined whether the AVP neurons were indeed activated as a result of the aging process in controls and AD patients. We applied a polyclonal antiserum directed against the medial cisternae of the GA on formalin-fixed, paraffin-embedded tissue sections taken from the dorsolateral SON (dl-SON) of 10 controls and 10 AD patients, and performed our measurements in this area that is known to be predominantly occupied (90-95%) by AVP neurons. In addition, the sparse OXT cells present in the area of study, were excluded from the measurements on the basis of alternative sections stained for OXT. In the dl-SON, the area occupied by the GA and the cellular profile area per patient were quaNtified by means of image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Golgi Apparatus
- Humans
- Immunohistochemistry
- Microscopy, Immunoelectron
- Middle Aged
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Supraoptic Nucleus
1. Previous studies suggest that arginine vasopressin (AVP) is released into the ventral septal area (VSA) of the rat brain during the antipyresis induced by the cyclo-oxygenase inhibitor indomethacin. In addition, there is evidence for increased AVP transmission in the VSA of animals having a reduced pyretic response following three intravenous injections of bacterial endotoxin (LPS) (endotoxin tolerant). Since ventral septal AVP receptors can also become 'sensitized' following exposure to AVP, we questioned whether the antipyretic action of indomethacin would increase, via an action involving central AVP, if this drug were administered into LPS-tolerant rats. 2. Intraperitoneal indomethacin (7.5 mg kg-1) was effectively antipyretic when administered 2 h after an intravenous challenge with LPS (50 micrograms kg-1) into conscious unrestrained rats. This dose of indomethacin had no effect on the core temperature of non-febrile rats given intravenous 0.9% pyrogen-free saline. 3. Three intravenous injections of LPS over a period of 3 days resulted in rats that were tolerant to the pyrogenic effects of LPS. When indomethacin was administered 2 h following the third LPS injection, a dose-dependent hypothermia was observed. This effect was age dependent, as profound hypothermia was seen in 8 week but not 20 week old rats. 4. A mortality rate of 41% (P = 0.02) was observed within 24 h of indomethacin treatment in 8 week old tolerant rats compared with 0% in 8 week old non-tolerant and 20 week old tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Antidiuretic Hormone Receptor Antagonists
- Arginine Vasopressin
- Body Temperature Regulation
- Dose-Response Relationship, Drug
- Drug Tolerance
- Escherichia coli
- Indomethacin
- Lipopolysaccharides
- Male
- Rats
- Rats, Sprague-Dawley
- Vasopressins
Adult golden hamsters, as compared to rats, lack several parvicellular vasopressinergic cell groups. We looked at the development of the vasopressinergic system in hamsters to draw comparisons with maturing rats. Arginine-vasopressin-immunoreactive (AVP-ir) neurons, their fibers and associated AVP binding sites were observed at several intervals after birth. Different rates of maturation were observed between different populations of vasopressinergic neurons. Within the suprachiasmatic nucleus (SCN), small AVP-ir neurons, their fibers and related binding sites maturated gradually during the first month after birth. In comparison, large AVP-ir neurons were apparent in newborn animals. Similarly, AVP-ir fibers and AVP binding sites were also present in the brain of newborns within areas not related to small vasopressinergic neurons from the SCN, such as the central amygdala (CeA) or the cerebral cortex. During the following weeks, a heterogenous pattern of development was observed within such areas. As the neurosecretory vasopressinergic system appeared to develop gradually, projections to the brain and their associated binding sites developed rapidly during the first week of life. Transient patterns of maturation were observed within certain sites. Indeed, some of the labelling observed in newborns regressed later. As similar reports were made in rats, our observations draw analogies between the vasopressinergic systems of these two species, beside their apparent dissimilarities in adult animals. Furthermore, our data also reinforce the concept that large vasopressinergic neurons do not constitute a homogenous population.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Cricetinae
- Female
- Male
- Mesocricetus
- Receptors, Vasopressin
- Species Specificity
The various hypothalamic nuclei show very different patterns of change in ageing. These patterns are a basis for changes in biological rhythms, hormones, autonomous functions or behavior. The suprachiasmatic nucleus (SCN) coordinates circadian and circannual rhythms. A marked seasonal and circadian variation in the vasopressin (AVP) cell number of the SCN was observed in relation to the variation in photoperiod. During normal ageing, the circadian variation and number of AVP-expressing neurons in the SCN decreases. The sexually dimorphic nucleus (SDN), intermediate nucleus or INAH-1 is localized between the supraoptic and paraventricular nucleus (PVN). In adult men the SDN is twice as large as in adult women. In girls, the SDN shows a first period of decreasing cell numbers during prepubertal development, leading to sexual dimorphism. During ageing a decrease in cell number is found in both sexes. The cells of the supraoptic nucleus and PVN produce AVP or oxytocin and coexpress tyrosine hydroxylase. These nuclei are examples of neuron populations that seem to stay perfectly intact in ageing. Parvicellular corticotropin-releasing-hormone (CRH)-containing neurons are found throughout the PVN. CRH neurons in the PVN are activated in the course of ageing, as indicated by their increase in number and AVP coexpression. Part of the infundibular (or arcuate) nucleus, the subventricular nucleus, contains hypertrophic neurons in postmenopausal women. The hypertrophied neurons contain neurokinin-B (NKB), substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The NKB neurons may also be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis might be involved in feeding behavior and metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Arcuate Nucleus of Hypothalamus
- Female
- Humans
- Hypothalamus
- Male
- Paraventricular Hypothalamic Nucleus
- Sex Characteristics
- Suprachiasmatic Nucleus
The total number of immunocytochemically identified vasopressin (AVP) cells was determined morphometrically in the paraventricular (PVN) and dorsolateral part of the supraoptic nucleus (dl-SON) of the human hypothalamus in 30 subjects ranging in age from 15 to 97 years, including 10 Alzheimer's disease (AD) patients. The aim of the present study was to test the hypothesis that the increased activity of AVP neurons reported earlier is accompanied by an absence of cell loss in these nuclei in senescence and AD. The results show that numbers of immunoreactive AVP cells in the PVN and dl-SON do not decline during aging or in AD. During aging, the number of neurons expressing AVP even increased in the PVN of control subjects. The nuclear diameter of the AVP cells in the PVN and dl-SON showed an increase in old AD patients. It is concluded that no cell loss occurs in the AVP cell population in the PVN and dl-SON during aging and in AD, and that AVP expression increases in the PVN during normal aging, but not in AD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Cross Reactions
- Female
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Neurons
- Paraventricular Hypothalamic Nucleus
- Supraoptic Nucleus
Developmental changes in the abundance, localization, and distribution of corticotropin-releasing hormone (CRH) mRNA and arginine vasopressin (AVP) mRNA in the ovine hypothalamus were examined by in situ hybridization. The effects of fetal hypoxemia in the presence or absence of concomitant cortisol in late gestation (day 135) were also investigated. CRH and AVP mRNA were present at low levels within the paraventricular nucleus (PVN) and AVP mRNA was present in the supraoptic nucleus (SON) by day 60 (full term = 147 days). During late gestation, there were increases (P < 0.05, days 140-143 vs. days 100-120) in CRH mRNA, a further increase (P < 0.05, full term vs. days 140-143) at full term (fetuses delivered in active labor), and a subsequent decline postpartum (compared with full term). AVP mRNA in the magnocellular PVN increased (P < 0.05) in late gestation, levels did not change in parvocellular fields compared with full term fetuses, but magnocellular and parvocellular AVP mRNA increased in the newborn (P < 0.05, newborn vs. full term). AVP mRNA in the SON showed a developmental profile similar to that of the PVN, although there was an increase earlier in gestation (P < 0.05, days 100-120 vs. days 60-80). Hypoxemia caused increases (P < 0.05) in CRH mRNA, plasma adrenocorticotropic hormone, and cortisol concentrations, and although magnocellular and parvocellular AVP mRNA appeared elevated, changes just failed to attain significance. Cortisol infusion attenuated the hypoxemia-induced increase in CRH mRNA and adrenocorticotropic hormone but was without effect on basal CRH mRNA levels.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Corticotropin-Releasing Hormone
- Embryonic and Fetal Development
- Female
- Fetus
- Gene Expression Regulation
- Gestational Age
- Hydrocortisone
- Hypoxia
- In Situ Hybridization
- Paraventricular Hypothalamic Nucleus
- Pregnancy
- RNA, Messenger
- Reference Values
- Sheep
Aging, as well as some frequently associated pathological conditions (depression, dementia, Alzheimer's disease, etc.), has been shown to have a profound impact on the normal functioning of the hippocampus-hypothalamo-pituitary-adrenocortical axis system. The hypothalamo-pituitary-adrenocortical axis in the aged rat is characterized by an increase in the basal level of circulating corticosterone, an impaired ability to recover from the adrenocortical stress response, and a reduced sensitivity to the dexamethasone suppression test. All these alterations may arise from a reduced hippocampal negative feedback control of the axis, as suggested by the age-dependent loss of hippocampal adrenocorticoid receptors. Among the hypothalamic corticotropin secretagogues, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) are considered the main physiological mediators of hypothalamic control of ACTH release. Thus, we have investigated the dynamic and the temporal course of the adrenocortical response to CRH and AVP in the aged rat. Freely moving jugular-catheterized male Sprague-Dawley rats (3- and 24-month-old) were injected with CRH (0.5, 0.05 and 0.01 microgram/kg i.v.), or AVP (1.0, 0.1 and 0.05 microgram/kg i.v.), or CRH and AVP in combination. In addition, adrenocortical sensitivity to corticotropin has been studied by injecting ACTH (10 ng/kg i.v.). Our study has (1) indicated that the response to ACTH secretagogues is dampened with aging, and (2) shown in the aged rat a slower recovery. Moreover, the results had confirmed the age-dependent increase in the basal level of corticosterone in the rat, and shown no age-related differences in the glucocorticoid response to ACTH.
MeSH Terms
- Adrenocorticotropic Hormone
- Age Factors
- Aging
- Animals
- Arginine Vasopressin
- Corticosterone
- Corticotropin-Releasing Hormone
- Glucocorticoids
- Injections, Intravenous
- Male
- Rats
- Rats, Sprague-Dawley
- Time Factors
The distribution of various vasoactive agents [nitric oxide synthase (NOS)- type I, endothelin-1 (ET-1), arginine-vasopressin (AVP), serotonin (5-HT), histamine and substance P (SP)] in the thoracic aortic endothelium of aged Sprague-Dawley rats was investigated using electron microscopic immunocytochemical methods. The aged thoracic aortic intima was characterized by a large number of leukocytes that adhered to the endothelium, an accumulation of a flake-like precipitate and clusters of leukocytes and smooth muscle cells (SMC) in the subendothelium. Age-associated alterations were also seen in the medial and adventitial layers of the vascular wall. An extensive vasa-vasorum was present in the adventitia from which leukocytes penetrated into perivascular tissue. Some vasa-vasorum showed mast cells adhered to perivascular pericytes. Immunocytochemistry showed about 70% endothelial cells (EC) with positive immunostaining for the brain isoform NOS-type I, compared to 10% in adult mature rats. About 10% of cells showed a positive immunoreaction for ET-1, which is about the same as for the mature adult thoracic aorta (8-9%). Subendothelial macrophages often showed positive immunostaining for antibodies against ET-1. The percentage of EC immunopositive to AVP, 5-HT, and histamine was 16-18, 15 and 12%, respectively compared to 5-8, 7-8 and 6% in mature adult rats. A few cells showed an immunopositive reaction for SP. In summary, the ageing vessel was characterized by a large number of leukocytes adhering to the endothelium and also by the presence of many macrophages and SMC in the subendothelial layer. The percentage of EC in rat thoracic aorta showing NOS immunostaining increased substantially from 10% in mature rats to 70% in aged rats. The percentage of EC immunopositive for AVP, 5-HT and histamine also increased about twofold compared to mature adult rats, while no changes were seen for ET-1.
MeSH Terms
- Aging
- Animals
- Aorta, Thoracic
- Endothelins
- Endothelium, Vascular
- Immunohistochemistry
- Male
- Microscopy, Electron
- Microscopy, Electron, Scanning
- Neurotransmitter Agents
- Nitric Oxide Synthase
- Rats
- Rats, Sprague-Dawley
Detection of the neurohypophysial hormones vasopressin (AVP) and oxytocin (OT) in the testis of several species has led to the proposal that these peptides may have a physiological role in the regulation of testicular function. Therefore, we investigated whether the contractile myoid cells of rat seminiferous tubules express functional receptors for AVP or OT and, thus, constitute a target for these hormones. This study used primary cultures of purified peritubular myoid cells derived from rats both before and after puberty. By several criteria, myoid cells prepared from adult rats expressed vasopressin receptors (VPRs). We detected specific and saturable [3H]AVP binding to a single population of sites with a Kd of 7.5 nM and a binding capacity of 145 fmol/mg protein. AVP stimulated the accumulation of inositol phosphates in a dose-dependent manner with an EC50 of 1.7 nM. Cloning and sequencing of the myoid cell VPR confirmed it to be the V1a subtype of VPR. VPR expression by myoid cells is under developmental control, as the receptors are present in the adult rat, but absent before puberty. In contrast, OT receptors were not expressed at any stage of development. Peritubular myoid cells are also responsive to endothelin-1 (ET-1), which potently stimulated phosphoinositidase-C. However, unlike AVP, the ET-1 responses were observed both before and after sexual maturity, suggesting different roles for AVP and ET-1 in the control of myoid cell function. Our data establish that the myoid cells of the adult rat seminiferous tubule are a target for AVP. This indicates an additional role for AVP in the regulation of testicular function and male fertility in the adult rat.
MeSH Terms
- 1-Methyl-3-isobutylxanthine
- Adenylyl Cyclases
- Aging
- Amino Acid Sequence
- Animals
- Arginine Vasopressin
- Base Sequence
- Blotting, Northern
- Cells, Cultured
- Cloning, Molecular
- Colforsin
- Consensus Sequence
- Cyclic AMP
- DNA Primers
- Gene Expression Regulation
- Inositol Phosphates
- Male
- Molecular Sequence Data
- Muscle, Smooth
- Phosphoric Diester Hydrolases
- Rats
- Rats, Wistar
- Receptors, Vasopressin
- Seminiferous Tubules
- Sequence Homology, Amino Acid
- Sexual Maturation
- Signal Transduction
- Testis
Medullary collecting tubules of rabbits were dissected from the outer zone at different stages of ontogenetic evolution and perfused in vitro. The hydraulic conductivity coefficient (Lp) was measured in the presence of either hypotonic perfusate and isotonic bath or isotonic perfusate and hypertonic bath. Basal Lp (cm s-1 atm-1 10(-7) was 85 /- 34 (N = 17) during early functional differentiation of the outer medullary collecting tubule (e-OMCT), 36 /- 6 (N = 8) in the intermediate state (i-OMCT), and 10 /- 7 (N = 11) in the final, mature state of function (m-OMCT). Addition of supramaximal concentrations of arginine-vasopressin (AVP) to the bath increased Lp in i-OMCT (250 /- 36) and m-OMCT (327 /- 63) but did not activate the osmotic hydraulic conductance in e-OMCT (105 /- 27). In 11 studies, OMCT were analyzed using isotonic solutions as the perfusate and bath medium. The spontaneous transtubular voltage (PD) was lumen positive, 1.71 /- 0.3 in e-OMCT, lumen negative 2.43 /- 0.3 in i-OMCT, and 6.1 /- 0.4 in m-OMCT. AVP had no effect on PD in e- and i-OMCT but increased the PD significantly (P less than 0.025) to 9.2 /- 0.6 in m-OMCT. The results indicate that both hydraulic conductivity coefficient and transtubular voltage in the medullary collecting tubule are dependent upon epithelial ontogeny and, particularly, display differential responses to the antidiuretic hormone. The data suggest that the differentiation of water and ion transport in the medullary collecting tubule may contribute to the increasing efficacy of the medullary countercurrent system.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Cell Differentiation
- Epithelium
- Kidney Medulla
- Kidney Tubules
- Kidney Tubules, Collecting
- Osmotic Pressure
- Rabbits
- Water-Electrolyte Balance
Osmoreceptor sensitivity, as estimated by the plasma vasopressin (AVP) response to hypertonic saline infusion, increases with age. We studied volume-pressure sensitivity, as estimated by the plasma AVP response to orthostasis, in healthy young (19-31 yr old; n = 12) and old (62-80 yr old; n = 15) subjects. After remaining recumbent overnight (minimum of 8 h), subjects stood quietly for 8 min. Cardiovascular changes on standing were not influenced by age. The peak plasma AVP response was greater in the young than in the old (P = 0.02, by rank sum test). When categorized as responders (peak AVP response, greater than or equal to 3 pg/ml) or nonresponders (peak response, less than 3 pg/ml), the young group included 11 responders and 1 nonresponder, while the old group included 8 responders and 7 nonresponders (P = 0.03, by Fisher exact test). There was no difference in the marked increase in plasma norepinephrine on standing between old responders (n = 6) and old nonresponders (n = 4). These studies indicate that failure to release AVP in response to orthostasis is more common in the elderly than in the young. The intact norepinephrine response to orthostatis in the elderly, regardless of the AVP response, suggests that the age-related defect is distal to the vasomotor center in the afferent limb of the baroreceptor reflex arc. Insensitivity to the volume and pressure changes accompanying hypertonic saline infusion may contribute to the previously noted augmented AVP response of the elderly to hyperosmolality.
MeSH Terms
- Adult
- Aged
- Aging
- Blood Pressure
- Blood Volume
- Humans
- Middle Aged
- Norepinephrine
- Osmolar Concentration
- Posture
- Pulse
- Vasopressins
- Water-Electrolyte Balance
In stroke-prone spontaneously hypertensive rats (SHRSP) and in normotensive Wistar-Kyoto rats (WKY), arginine vasopressin (AVP) was measured by means of a radioimmunoassay in the plasma, the pituitary gland, the hypothalamus, and the brain stem. In 6- and 14-wk-old SHRSP, the plasma concentration of AVP was lower than in age-matched WKY (P less than 0.01), whereas it was elevated at 28 wk of age (P less than 0.01). In the pituitary of 6-wk-old SHRSP, AVP was higher than in WKY (P less than 0.05), but no such difference was found in older rats. In the hypothalamus and the brain stem, AVP content was reduced in all age groups of SHRSP. Plasma osmolality was diminished in 28-wk-old SHRSP only (P less than 0.01), whereas hematocrit in all age groups was higher in SHRSP than in WKY. It is concluded that the secretion of AVP and possibly its synthesis in the hypothalamus are reduced in SHRSP. Whether the reduced AVP content in the brain stem is related to the sustained elevation of blood pressure has to be studied further.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Blood Pressure
- Body Weight
- Brain Chemistry
- Hematocrit
- Hypertension
- Male
- Organ Specificity
- Pituitary Gland
- Rats
- Rats, Inbred Strains
The activity of the hypothalamo-neurohypophyseal system (HNS) was determined in male Wistar rats from 3 to 32 months of age. Plasma levels of vasopressin (AVP) and oxytocin (OXT) were measured by means of a radioimmunoassay. In addition, the distribution of the Golgi apparatus marker enzyme thiamine-pyrophosphatase (TPP-ase) was measured as a parameter for neurosecretory activity in the hypothalamic supraoptic and paraventricular nuclei (SON and PVN). Plasma levels of radioimmunoassayable AVP were increased in the 32-month-old animals. Plasma levels of radioimmunoassayable OXT in 32-month-old animals did not differ from the levels found in the youngest group, but were higher than in 11-month-old animals. Neurosecretory activity in the SON was similar in 3- and 32-month-old animals, whereas in the PVN neurosecretory activity was increased in the 32-month-old animals. Urine excretion decreased between 6 and 11 months of age and remained on the same level until 32 months of age. In other words, instead of a loss of HNS function as has been suggested in the literature, an increased neurosecretory activity was observed in aged rats.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Body Weight
- Brain
- Hypothalamo-Hypophyseal System
- Male
- Neurons
- Organ Size
- Oxytocin
- Radioimmunoassay
- Rats
- Rats, Inbred Strains
- Urine
The age-related time-course of changes in arginine-vasopressin (AVP) content in the pituitary gland was studied in adult intact Wistar rats. In 60-day-old rats, the hormone content was measured before and after 24 h of water deprivation. In adult rats treated with a single injection of hydrocortisone at different times after birth, the content of AVP remained high in rats injected with hydrocortisone on day 2 or day 5 after birth, exceeding significantly the content of AVP in intact rats. The animals injected with hydrocortisone on day 9 or 15 manifested a more noticeable reduction in the hormone content, as was the case in intact rats. It is suggested that the first five days after birth is a critical period in the formation of the central regulation of AVP secretion with high sensitivity to short-term changes in corticosteroid balance.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Chromatography, Liquid
- Hydrocortisone
- Pituitary Gland, Posterior
- Rats
- Rats, Inbred Strains
- Vasopressins
- Water Deprivation
We investigated the importance of arginine-vasopressin (AVP) for blood pressure control in young and adult rats. Most of the studies were performed on Brattleboro rats with complete diabetes insipidus (DI). In some protocols, Sprague-Dawley rats (SD) were also used. The rats were age 20-24 days (young) or 50-80 days (adult). Adult DI rats have a significantly higher mean arterial pressure (MAP) than adult SD rats. The studies were performed during normovolemia and hypovolemia. Hypovolemia was created by the rapid withdrawal of blood, 0.5-1.5% of body weight. Following bleeding 0.5% of the body weight, young DI rats had a significantly larger decrease in MAP than adult DI and young and adult SD rats. Continuous infusion of AVP (2000 pg X 100 g-1 min-1) blunted the hemorrhagic hypotension in the DI rats. In all groups of rats studied, AVP had little effect on the MAP during normovolemia. The effect of AVP (given in a bolus dose of 20 or 2000 pg X 100 g-1) on the MAP was in DI rats significantly related to the MAP immediately prior to the AVP administration. No effect on MAP was observed when the initial MAP was 105-112 mm in the young DI rats and 148-157 mm in the adult DI rats. The effect of AVP (20 pg X 100 g-1) appeared to be submaximal to maximal. In anaesthetized SD rats, the basal AVP production was higher in the young than in the adult animals. Following bleeding, serum AVP increased in both young and adult rats but the increase was significant only in the adult rats.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Blood Pressure
- Blood Volume
- Diabetes Insipidus
- Hemodynamics
- Rats
- Rats, Brattleboro
- Rats, Inbred Strains
Changes of magnocellular neurons after hypophysectomy were immunohistochemically studied using antisera to arginine vasopressin (AVP) and oxytocin (OXT) in young and old female mice of the C57BL/Tw strain. AVP-immunoreactive neurons in the supraoptic and paraventricular nuclei of intact 19-month-old mice showed a marked reduction in number and immunoreactivity as compared with those of intact 3-month-old mice. Age difference of OXT-immunoreactive neurons was less pronounced than that of AVP-immunoreactive neurons. After hypophysectomy, both AVP- and OXT-immunoreactive neurons showed an intense stainability 10 days after the operation regardless of ages. However, the rate of reduction in number of immunoreactive neurons after hypophysectomy was less marked in 19-month-old than 3-month-old mice.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Female
- Hypophysectomy
- Immunochemistry
- Mice
- Mice, Inbred C57BL
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Pituitary Gland
- Supraoptic Nucleus
The development of the ability of the kidney to concentrate urine was studied in normal and propylthiouracil-treated rats by measuring urinary sodium concentration and osmolarity at different ages. It was shown that the normal animals, but not the PTU-treated ones were able to concentrate urine at 35 days of age. The response of the hypothalamo-neurohypophyseal axis (AVP system) and that of the kidney were investigated in the two categories of animals at 35 days of age by measuring concomitantly the AVP content of the hypothalamus and neurohypophysis, the AVP plasma concentration and the natremia and plasma osmolarity at various intervals after intraperitoneal injection of a 5% NaCl solution. In normal, as well as in PTU-treated rats, salt load did not lead to significant modifications of the hypothalamic AVP content. In comparison with normal rats, the neurohypophysis of the PTU-treated ones released AVP more slowly, but with a similar amplitude. In normal rats, the plasma AVP concentration was already maximal 30 min after salt load and then decreased and returned to the normal value at 2 hrs; at the same time, the natremia and plasma osmolarity also recovered their normal value. In contrast, the plasma AVP concentration as well as the natremia remained high 1 h 30 after salt load in PTU-treated rats. It is concluded that PTU-treated young rat is unable to compensate the salt load in normal delays. Beside the slowing in AVP release by neurohypophysis and decreased AVP plasma level, the responsiveness of the kidney seems to be altered.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Hypothalamo-Hypophyseal System
- Kidney
- Kidney Concentrating Ability
- Male
- Natriuresis
- Osmolar Concentration
- Pituitary Gland, Posterior
- Propylthiouracil
- Rats
- Rats, Inbred Strains
- Sodium
- Sodium Chloride
The neuropeptides vasopressin (AVP) and oxytocin (OXT) are supposed to be involved not only in peripheral functions (e.g. diuresis, labour and lactation) but also in central processes that are frequently disturbed during aging and senile dementia (e.g. fluid and electrolyte homeostasis and cognitive functions). A concomitant decrease in activity of the hypothalamo-neurohypophyseal system (HNS) with aging has been postulated in the literature, but has not yet been established. In order to investigate possible age-related changes in the human HNS, immunocytochemically identified AVP and OXT neurons in the paraventricular and supraoptic nucleus (PVN and SON) were analysed morphometrically in subjects from 10 to 93 years of age, including patients with senile dementia of the Alzheimer type (SDAT). Cell size was used as a parameter for peptide production. Mean profile area of OXT cells did not show any significant changes with increasing age. Mean profile area of AVP cells, however, showed an initial decrease up to the sixth decade of life, after which a gradual increase was observed. Size of AVP and OXT cell nuclei did not change significantly with aging. Observations in brains from patients with SDAT were within the range for their age group. The present results do not support degeneration or diminished function of the HNS in senescence or SDAT, as generally presumed in the literature, but suggest an activation of AVP cells after 80 years of age. The activation of AVP cells in senescence is in accordance with previous findings in the aged Wistar rat.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Alzheimer Disease
- Arginine Vasopressin
- Child
- Female
- Histocytochemistry
- Humans
- Immunochemistry
- Male
- Middle Aged
- Neurons
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Supraoptic Nucleus
The effect of aging on the vasopressin (AVP) and oxytocin (OXT) innervation of the brain was studied by means of immunocytochemistry, comparing the major innervated areas in 5-month-old and 34-month-old male Brown-Norway rats. A marked decrease of AVP fiber density was found in the old rats as compared with the young animals in the vertical limb of the diagonal band, the basal nucleus of Meynert, the lateral habenular nucleus, the medial amygdaloid nucleus, the substantia nigra, the ventral hippocampus, the central gray, the locus coeruleus and in the ambiguus nucleus. The AVP innervation of the lateral septum and the dorsomedial hypothalamic nucleus was moderately, although not significantly reduced. No age difference in AVP innervation was found in the paraventricular thalamic nucleus or in the nucleus of the solitary tract. OXT fiber density did not differ between young and old animals in the locus coeruleus, the nucleus of the solitary tract and the ambiguus nucleus. Thus, the aging process appears to affect AVP cells in a differential, rather than in a general way. Changes were found to be more pronounced in those areas where the AVP innervation is dependent upon circulating androgens.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Brain
- Hippocampus
- Immunoenzyme Techniques
- Limbic System
- Locus Coeruleus
- Male
- Oxytocin
- Periaqueductal Gray
- Rats
- Substantia Innominata
- Substantia Nigra
A recent study has shown that vasopressin (AVP) cells in the human supraoptic (SON) and paraventricular (PVN) nuclei increase in size after 60 years of age, suggesting that AVP production is increased in senescence. In the present study, the same brain material was used for the determination of nucleolar size in immunocytochemically identified AVP and oxytocin (OXT) neurons as an additional parameter for peptide production. A strong correlation was found between nucleolar size and cell size, both in AVP and OXT neurons. Nucleolar size of AVP but not of OXT neurons increased significantly in senescence. Observations in brains from patients with senile dementia of the Alzheimer type (SDAT) were commensurate with their ages. These results strongly support the hypothesis that AVP neurons in the SON and PVN are activated in old age.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Cell Nucleolus
- Child
- Dementia
- Humans
- Immunoenzyme Techniques
- Middle Aged
- Oxytocin
- Paraventricular Hypothalamic Nucleus
- Supraoptic Nucleus
Neural lobe function in male rats of the Wistar/Tw strain was studied at 3, 7 and 16-18 months of age. A significant rise in the serum arginine vasopressin (AVP) level was noted in 16-18-month-old rats showing polydipsia and polyuria. The content and concentration of AVP in the neural lobe of aged rats were significantly less than those of younger animals (3 and 7 months). These results point out an enhancement of AVP release from the neural lobe of aged rats. The reduction in urinary volume in aged rats subjected to 24 hours of water deprivation was less than those in younger animals. No increase in urinary sodium, potassium and chloride concentrations was observed in aged rats, and the decrease in electrolyte excretion from urine during the dehydration period was less in aged rats than younger ones. These results suggest that the antidiuretic response to osmotic stimuli was reduced in aged rats. The administration of AVP to aged rats resulted in a significant decrease in water intake and urinary volume, but AVP administration did not induce any change in the electrolyte balance. Therefore, it is concluded that the main cause of the development of polydipsia and polyuria is the decline in renal function but not in neurosecretory activity, although exogenous AVP can effectively reduce water intake and urinary output in aged rats.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Chlorides
- Kidney
- Male
- Pituitary Gland, Posterior
- Polyuria
- Potassium
- Rats
- Rats, Inbred Strains
- Sodium
- Thirst
- Water Deprivation
- Water-Electrolyte Balance
Systemic injections of arginine vasopressin (AVP, 0.08 pressor units/kg i.p.) to mature rats (10-13 months) trained on a positively reinforced timing task prevented the age-related discrepancies in the content of temporal memory and the increases in sodium-dependent high affinity choline uptake (SDHCU) in the frontal cortex observed in control rats when the rats became aged (27-30 months). AVP administration had no effect on muscarinic receptor density as measured by [3H]quinuclidinyl benzilate (QNB) binding or on choline acetyltransferase (ChAT) levels in either the hippocampus or the frontal cortex.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Brain Chemistry
- Choline
- Male
- Memory
- Rats
- Rats, Inbred Strains
- Reinforcement Schedule
- Sodium
In male and female rats of two different age groups, we measured the arginine-vasopressin (AVP) levels in cerebrospinal fluid (CSF) collected at different times of the day. Mean values of AVP in cisternal CSF averaged across the different times of the day were higher in males than in females (p = 0.02), and in young (2 months) than in aged (12 months) rats (p = 0.03) of both sexes. The AVP levels in CSF showed a clear circadian rhythm in both young and aged male rats; the values at 07.00 h and 13.00 h were higher than those at 01.00 h and 19.00 h. The amplitude of the rhythm was smaller in females than in males. In addition, the rhythm was more pronounced in young than in aged rats of both sexes. These data suggest that both age and sex affect levels of vasopressin in CSF.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Circadian Rhythm
- Female
- Male
- Radioimmunoassay
- Rats
- Rats, Inbred Strains
- Sex Characteristics
The renal and vasopressin (AVP) response to a standard oral water load (20 ml/kg) was examined in a group of water-replete healthy elderly men (n = 6). Two groups, respectively, of water-replete and water-deprived young healthy volunteers acted as controls. After 2 h, the old group had excreted 41 /- 2.4% (mean /- SEM) of the water load compared to 100.7 /- 8.8% in the water-replete young group and 70 /- 3.8% in the water-deprived young group (P less than 0.01). Similarly, peak diuresis (7.01 /- 0.48 ml/kg) and peak free-water clearance (5.7 /- 0.48 ml/min) as determined from hourly sampling in the old group were delayed and significantly less than both young groups (P less than 0.01) (peak diuresis, young water-replete, 10.86 /- 0.56 ml/kg, young water-deprived, 10.2 /- 0.64 ml/kg, peak free-water clearance, young water-replete 8.4 /- 0.72 ml/min, young water-deprived 9.5 /- 0.88 ml/min). When these indices were adjusted for reduced creatinine clearance (Ccr) in the elderly, there was no significant difference between the young and old groups. Plasma AVP decreased similarly in all three groups following ingestion of water but there was no significant difference in mean plasma AVP between the young and old subjects throughout the study period. We therefore conclude that ability to excrete excess water promptly is impaired in healthy elderly men. This defect is due, at least in part, to an age-related reduction in glomerular filtration rate.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Arginine Vasopressin
- Blood Pressure
- Diuresis
- Humans
- Male
- Middle Aged
- Osmolar Concentration
- Sodium
- Thirst
- Water Deprivation
Disorders of water balance are common among elderly patients. A number of factors may contribute. Osmoreceptor-mediated release of AVP is increased, but the response to volume stimuli may be reduced. The capacity of the kidney to concentrate urine is reduced by age, but this impairment cannot be correlated with coincident loss of glomerular filtration (GFR); there may rather be a failure of cAMP response to AVP in aging kidneys. Free water clearance is reduced in the old in proportion to the loss of GFR. Thirst mechanisms are also significantly impaired in healthy as well as sick old people. This combination of factors renders old people particularly liable to develop disorders of water homeostasis during episodes of acute or chronic ill health.
MeSH Terms
- Aging
- Animals
- Body Water
- Humans
- Kidney
- Thirst
- Vasopressins
Osmoreceptor sensitivity is enhanced in healthy elderly subjects and AVP secretion is increased, relative to that of younger subjects, when plasma osmolality rises. Increased AVP secretion/unit increase in plasma tonicity reflects a decrease in collecting tubule sensitivity to AVP by an as yet unknown mechanism in the aged kidney. This change in sensitivity is not completely offset by increased ADH release, so that maximum Uosm achievable under hydropenic conditions (concentrating ability) is reduced in the elderly. CH2O in older subjects decreases in proportion to the fall in GFR; thus, CH2O is intact in older subjects with preserved GFR. In subjects with age-related reductions in GFR, minimal Uosm achievable is usually less than 100 mOsm per kg H2O and thus usually sufficient to meet the demands of solute-free water intake so that plasma hypo-osmolarity does not result. Increasing exposure of the elderly to pharmacologic agents that reduce CH2O is primarily responsible for the impression that aged patients are at increased risk for hyponatremia.
MeSH Terms
- Adult
- Aged
- Aging
- Arginine Vasopressin
- Body Water
- Diuresis
- Humans
- Kidney Concentrating Ability
- Kidney Tubules
- Middle Aged
- Osmolar Concentration
- Urine
- Water-Electrolyte Balance
Chronically catheterized fetal lambs (n = 11, gestational age 111-139 days) and neonatal lambs (n = 20, postnatal age 4-30 days) were studied to explore during development the relationship of renal hemodynamic responses during hypoxemia to plasma epinephrine concentration (E), plasma norepinephrine concentration (NE), plasma arginine vasopressin concentration (AVP), and plasma renin activity (PRA). A low oxygen gas mixture (11.1 /- 0.1% O2) was administered for 30 min to the pregnant ewe or neonatal lamb to induce hypoxemia with maintenance of normal arterial pCO2 and pH. Arterial blood pressure was recorded continuously and renal blood flow (RBF) was determined by the radiolabeled microsphere technique. Moderate hypoxemia (pO2 16 /- 2 torr and 33 /- 6 torr in fetus and neonate, respectively) induced increases in E, NE (measured by radioenzymatic assay), and AVP (measured by radioimmunoassay) in both fetus and neonate. PRA (measured by radioimmunoassay) also increased in response to hypoxemia in neonatal lambs. The change in mean arterial pressure with hypoxemia (delta MAP) was significant in fetuses (delta MAP 8 /- 14%, p less than 0.05) but not in lambs (delta MAP 1 /- 10%, p greater than 0.5). Similarly, the change in renal blood flow with hypoxemia (delta RBF) was significant (delta RBF -51 /- 24%, p less than 0.001) in fetuses but not in neonatal lambs (delta RBF -9 /- 38%, p greater than 0.1). These results reflected a change in renal vascular resistance with hypoxemia (delta RVR) that was significant in fetal lambs (delta RVR 169 /- 168%, p less than 0.01) but not in neonatal lambs (delta RVR 51 /- 180%, p greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Blood Pressure
- Epinephrine
- Female
- Fetus
- Hypoxia
- Norepinephrine
- Pregnancy
- Regression Analysis
- Renal Circulation
- Renin
- Sheep
- Vascular Resistance
- Vasoconstrictor Agents
The relationship of plasma levels of adrenaline, noradrenaline, arginine vasopressin (AVP) and plasma renin activity (PRA) to heart rate were studied in normoxaemic and hypoxaemic fetal, neonatal and adult sheep. The mean heart rate response of fetuses at the end of a 30 minute period of 10% oxygen delivery to the maternal ewe was tachycardia. However bradycardia, usually of a transient nature, was observed in 9 of the 12 fetuses (P less than 0.05). Multiple regression analysis was used to determine the contribution of blood gas, blood pressure and plasma hormone levels to the variance in heart rate in the perinatal sheep. 22% of the variance in fetal heart rate was provided by PRA and age from conception (P less than 0.001). Tachycardia was the invariable heart rate response of the neonates and adults to hypoxaemia. 61% of the variance in neonatal heart rate was contributed by PaO2, PaCO2, AVP, PRA and systolic blood pressure (SBP, P less than 0.001). PaO2 and plasma levels of adrenaline were significantly related to adult heart rate (P less than 0.001). Those fetuses which developed bradycardia had lower PaO2 but higher AVP and PRA during hypoxaemia than those which did not develop bradycardia. The major determinant of the area of the fetal bradycardia response was found, by multiple regression analysis, to be plasma adrenaline concentration (P less than 0.05). Thus different hormonal factors may play a role in the regulation of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Carbon Dioxide
- Embryonic and Fetal Development
- Epinephrine
- Fetal Blood
- Heart Rate
- Norepinephrine
- Oxygen
- Renin
- Sheep
The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the possibility of restoring central AVP innervation by peripheral testosterone supplementation was investigated by giving senescent (33 months) Brown-Norway rats subcutaneous implants of either empty or testosterone-filled silastic tubes for the period of 1 month. Plasma testosterone levels of testosterone-treated animals were restored to values which did not differ from those of young animals. The results show that the age-related decline in AVP fiber density can indeed be reversed by testosterone supplementation. In contrast, oxytocin innervation, which was previously shown not to be testosterone-dependent, was not restored. These results show for the first time restoration of a specific innervation pattern in the senescent rat brain mediated by peripheral hormones and indicate that a considerable plasticity is retained in the aging central nervous system.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Brain
- Drug Implants
- Immunoenzyme Techniques
- Organ Specificity
- Oxytocin
- Radioimmunoassay
- Rats
- Reference Values
- Testosterone
We have compared the biological (B) and immunological (I) ACTH-like activities (ALA) released by short term cultured pituitary cells from fetal (63-144 days old) and young lambs (7-150 days old) both under basal conditions, and when stimulated by ovine(o)CRF-(1-41) or arginine vasopressin (AVP), separately or in combination. The bioassay was based on the production of corticosteroids by cultured adrenal cells from adult sheep. The standard used in both the RIA and the bioassay was synthetic ACTH-(1-24). Under every condition, curves for dilution of the incubation media were parallel to the standard curves in both the RIA and the bioassay. When expressed per 5 X 10(5) pituitary cells, B-ALA output increased with gestational age and remained high after birth. During fetal life, B-ALA released was always lower than I-ALA. However, the B/I ratios increased with gestational age from 0.29 /- (SE) 0.04 at 63 days to 0.70 /- 0.04 at 144 days. Conversely, for postpartum animals, the B/I ratios were not different from 1, except in the case of stimulation by AVP alone, when they were significantly higher than 1.A 4-day treatment of pituitary cells from 120- to 126-day-old fetuses by AVP or cortisol resulted in an 1.5-fold enhancement of the B/I ratio of the ALA secreted under AVP stimulation. These results indicate that during development of the sheep I-ACTH levels are probably not representative of the corticotropic activity released by the pituitary. Furthermore, they suggest that the prepartum increase in fetal cortisol does result, in part, from an enhanced tropic drive to the fetal adrenal.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Cells, Cultured
- Fetus
- Gestational Age
- Hydrocortisone
- Pituitary Gland
- Radioimmunoassay
- Sheep
Fetal adaptation to the extrauterine environment is associated with profound alterations in pulmonary, renal, and cardiovascular functions. Coincident with these changes are a variety of endocrine responses including concomitant increases in plasma catecholamine and arginine vasopressin (AVP) levels. In view of the demonstrated interaction between the sympathoadrenal system and the neurohypophysis in adult mammals, we questioned whether increases in plasma catecholamine levels in the fetus affect fetal plasma AVP levels and whether catecholamine-AVP interactions change developmentally. Chronically catheterized fetal lambs at either 131 /- 1 (preterm) or 142 /- 1 days (term) received graded infusions of either epinephrine (E) or norepinephrine (NE) at rates of 0.04, 0.2, 0.75, 1.5, and 3.0 micrograms.min-1.kg-1 during successive 40-min infusion periods. Plasma AVP concentrations in term animals significantly increased (1.4 /- 0.1 to 5.1 /- 1.6 pg AVP/ml) in response to E infusion of 0.75 microgram.min-1.kg-1 or greater. The log-linear dose response curves for each animal were used to determine the minimum plasma E concentration required to stimulate AVP secretion or "threshold." The mean plasma E threshold for AVP secretion was significantly lower in term animals (1.4 /- 0.4 ng/ml) than in preterm animals (6.6 /- 0.9 ng/ml). Plasma E levels were positively correlated with plasma AVP levels (r = 0.90) above the threshold value in both groups. Changes in plasma AVP levels were observed in preterm or term animals in response to NE only at the highest infusion rate studied.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Blood Pressure
- Embryonic and Fetal Development
- Epinephrine
- Female
- Fetal Blood
- Fetus
- Heart Rate
- Norepinephrine
- Pregnancy
- Sheep
Young, middle-aged and aged rats received s.c. testosterone implants for 50-52 days in order to investigate whether supplementation of testosterone in aged rats could normalize the reported reduction of kidney arginine vasopressin (AVP)-binding sites and increase the plasma concentration of AVP. Receptor number, which was measured by means of a membrane-binding assay with [3H]AVP as ligand, was below the detection level in the untreated aged rat. Following testosterone treatment, no effects were seen in the youngest groups, but in the aged group AVP receptors became clearly detectable, albeit with a lower affinity. A remarkable observation was the increase in affinity for renal AVP binding in the middle-aged compared with the young rat. Plasma levels of AVP in control aged rats tended to be higher. Such a tendency was completely absent in the testosterone-treated aged rats. Possible mechanisms underlying the restoration of reduced AVP-binding sites in the kidney of the aged rat by testosterone treatment are discussed.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Binding Sites
- Kidney
- Male
- Osmolar Concentration
- Rats
- Rats, Inbred BN
- Receptors, Angiotensin
- Receptors, Vasopressin
- Testosterone
Corticotropin-releasing factor-like immunoreactivity (CRF-LI), arginine vasopressin-like immunoreactivity (AVP-LI) and ACTH-releasing bioactivity of hypothalamic tissue from 63- to 143-day-old ovine fetuses and from 7- and 150-day-old lambs have been assessed. CRF-LI and AVP-LI contents and concentrations increased steadily between 63 and 138 days of gestation, decreased at day 143 then rose again in postpartum animals. In terms of concentration, the AVP-LI/CRF-LI ratio remained close to 5 between 63 and 123 days of intrauterine life, decreased steadily in late gestation down to 1.2 at day 143 increased again in lambs. The total hypothalamic ACTH-releasing bioactivity increased 26-fold between 63 and 138 days of gestation and remained constant until day 143. The highest values were observed in 150-day-old-lambs. These data support the view that AVP and oCRF1-41 might be important hypothalamic factors involved in the regulation of ACTH release by the pituitary gland of the sheep fetus. In addition, they suggest that AVP is more important in young fetuses and lambs than in prepartum animals.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Corticotropin-Releasing Hormone
- Embryonic and Fetal Development
- Hypothalamus
- Sheep
The steroidogenic response of purified Leydig cells from mice at various ages (from 10-95 days old) was investigated after exposure of cells to arginine vasopressin (AVP) or oxytocin (OT). A 24-h pretreatment by the neurohypophysial hormones significantly increased the acute (3-h) testosterone production by 1.3- to 3-fold at all ages studied, with the exception of pubertal Leydig cells which responded with a 5- to 7-fold increment of testosterone production (P less than 0.05). The higher responsiveness of pubertal Leydig cells to AVP does not result from an increased sensitivity, since the half-maximal effective doses (ED50) of AVP needed to stimulate testosterone production were quite similar and were in nanomolar range for both pubertal and adult Leydig cells. In addition, the ED50 for OT was 10 times higher than that for AVP. Cycloheximide totally abolished the AVP stimulation, suggesting that the AVP effect is dependent upon new protein synthesis. No modification of hCG-stimulated testosterone production occurred after a 24-h pretreatment of Leydig cells by AVP or OT for all ages studied. A 72-h AVP pretreatment resulted in a marked decrease (50-60%) in acute hCG-stimulated testosterone production in both pubertal and adult Leydig cells. Binding studies of [3H]AVP to purified Leydig cells from prepubertal, pubertal, and adult mice showed the presence of a single set of high affinity V1 sites. The Kd values, in the nanomolar ranges, remained unchanged regardless of age. Maximal capacities were of the same order in the prepubertal and adult Leydig cells (9,460 vs. 10,314 sites/cell), while a 50% decrease (P less than 0.01) in the number of AVP receptors occurred in pubertal Leydig cells (5,048 sites/cell). These data indicate developmental changes in the steroidogenic responsiveness of Leydig cells to neurohypophysial hormones and suggest that AVP receptors might be under a regulatory mechanism(s) during puberty. They provide additional evidence for participation of neurohypophysial hormones in autocrine/paracrine regulation of testicular steroidogenesis.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Cycloheximide
- Dose-Response Relationship, Drug
- Leydig Cells
- Male
- Mice
- Mice, Inbred Strains
- Oxytocin
- Receptors, Angiotensin
- Receptors, Vasopressin
- Testosterone
Autoradiographic analysis of 1, 8, 16 and 26-day-old rat brains showed 3H-arginine8-vasopressin (3H-AVP) binding to the cingulate gyrus-dorsal hippocampus (CG) only in the 8-day-old rat brain. Saturation analysis of CG membranes prepared from pups (7-10 days) and adults (90 days) revealed a small but significant increase in binding site concentration in adults compared to pups. However, the Kd of the 3H-AVP binding site increased significantly with age. The Kd of 3H-AVP binding to pup CG membranes was 0.9 /- 0.1 nM, while the adult CG was 5.7 /- 1.0 nM. The pharmacological specificity of 3H-AVP binding sites in the pup and adult CG was similar, but differed markedly from the profile observed in adult septal membranes. The primary specificity difference between the pup CG and septum was the reduced potency of certain V1 receptor antagonists. In competition experiments the CG binding site showed a reduced affinity for the V1 antagonist, [d(CH2)5, Tyr(Me)]AVP. This reduced affinity for the V1 antagonist was also documented autoradiographically using 3H-[d(CH2)5, Tyr(Me)]AVP. The data suggest that the 3H-AVP binding site expressed in the pup CG is not identical to the V1 type receptor present in the periphery and brain of the adult rat.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Autoradiography
- Binding, Competitive
- Female
- Gyrus Cinguli
- Male
- Radioligand Assay
- Rats
- Rats, Inbred Strains
- Receptors, Angiotensin
- Receptors, Vasopressin
The antidiuretic activity of an arginine vasotocin (AVT) solution (10 microU/ml) was studied in comparison with an arginine vasopressin (AVP) solution (10 microU/ml) after their incubation for 1 h at 37 degrees C with the supernatants (S) or the pellets (P) of the habenular nuclei (HN) or frontal cortex (FC) fragments homogenized in saline solution, removed from adult or newborn rats. Both SHN and SFC from adults inactivated about 5 microU/ml AVT and 10 microU/ml AVP, PHN and not PFC inactivated only about 7 microU/ml. In newborns the phenomena were in the same direction, but the specific inactivation of AVT by the PHN was of about twice greater than in adults. The results are interpreted as suggesting that, in contrast to an unspecific inactivation from S, probably of an enzymatic nature, the PHN specifically bind AVT and that this activity is greater in newborn than in adult rats.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Arginine Vasopressin
- Frontal Lobe
- Rats
- Rats, Inbred Strains
- Receptors, Angiotensin
- Receptors, Vasopressin
- Thalamic Nuclei
- Vasotocin
The ontogeny of oxytocin receptors in rat forebrain was studied using the selective oxytocin receptor antagonist 125I-d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH29]OVT [( 125I]-OTA). With in vitro receptor autoradiography, binding wa noted on the first postnatal day in dorsal subiculum and thalamus. On postnatal days 5-18, intense labeling was evident in posterior cingulate cortex, dorsal subiculum, lateral septum, and the CA1 subfield of hippocampus. Of these regions only the lateral septum expressed oxytocin receptors in adult brain. Competition studies on coronal sections through posterior cingulate, septum, and dorsal subiculum at P10 demonstrated that transient binding sites in these areas were indeed oxytocin selective (OXY greater than AVP greater tha V1 greater than V2). Result of saturation studies on cingulate membranes from 10-day-old pups agreed favorably with previous reports of the kinetics of [125I]-OTA binding to adult oxytocin receptors (Kd = 0.1 nM in P10 cingulate cortex vs. 0.07 nM for adult ventral subiculum). In contrast to these evanescent developmental sites, oxytocin receptors in the bed nucleus of the stria terminalis and the ventromedial nucleus of the hypothalamus only appeared in adulthood, presumably in response to the surge of gonadal steroids at puberty.
MeSH Terms
- Aging
- Animals
- Binding, Competitive
- Frontal Lobe
- Oxytocin
- Rats
- Rats, Inbred Strains
- Receptors, Angiotensin
- Receptors, Oxytocin
The expression of 3 neuropeptide genes, vasopressin (AVP), oxytocin (OT) and somatostatin (SOM), was studied in the developing rat hypothalamus using Northern blot analysis combined with densitometric scanning. A unique profile of developmental expression was established for each of the 3 genes. SOM mRNA is detectable at embryonic day 14 and reaches 40% of the adult levels by embryonic day 18. By contrast, accumulation of AVP and OT mRNA is mainly a postnatal event. AVP mRNA, although detectable in the late embryo, rises gradually after birth and attains 40% of adult levels after the second postnatal week. Maturation of OT gene expression occurs even later and parallels AVP gene expression with a lag time of one week. Observed increases in mRNA levels are due to an upregulation of gene expression since they occur essentially following cessation of neuronal cell proliferation. The rise in AVP and OT mRNA accumulation coincides with the establishment of synaptic input to AVP and OT neurons. Expression of the SOM gene, by contrast, occurs prior to neuronal cell differentiation and points to a possible function of SOM in the embryonic brain.
MeSH Terms
- Aging
- Animals
- Gene Expression Regulation
- Hypothalamus
- Oxytocin
- RNA, Messenger
- Rats
- Rats, Inbred Strains
- Somatostatin
- Vasopressins
Imbalance of water and electrolytes in the elderly was investigated. In the elderly, hyponatremia is the most common electrolyte imbalance disorder and half of the cases with hyponatremia are accompanied by malignancy. It is well known that renal function decreases with ageing, and hyporeninemic hypoaldosteronism, relative AVP unresponsiveness and high level of plasma ANP are observed in the elderly. Therefore, renin-aldosterone system, AVP and ANP as well as renal function of the elderly were studied. AVP response to osmotic stimulus in the elderly increased, indicating that osmostat hypersensitivity existed in the elderly. The response of ANP to hypertonic saline infusion was well preserved. Increase in FENa with decrease in GFR and decreased salt-retaining renal capacity, with low response of the renin-aldosterone system, under low salt intake were observed in the elderly. Therefore, the low response of renin-aldosterone system may be, in part, involved in the pathophysiology. Plasma ANP positively correlated with FENa and the rate of the response of FENa to endogenous ANP was lower in the elderly than in young adults. In addition, the ANP disappearance rate from plasma in the elderly decreased. It was, therefore, suggested that those factors might be, in part, responsible for the increase in plasma ANP level. Accordingly, a high plasma ANP level might be relatively non-contributory to hyponatremia in the elderly. In summary, hyponatremia is the most common disorder of electrolyte imbalance in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aged
- Aging
- Arginine Vasopressin
- Atrial Natriuretic Factor
- Humans
- Renin-Angiotensin System
- Water-Electrolyte Imbalance
The data on the development of molecular mechanism of the antidiuretic effect of vasopressin and the molecular structure of the AVP receptor, cytosolic cAMP-dependent protein-kinases and renal response to AVP, are discussed. The experiments were performed in normal rats and mice, nephrogenic diabetes insipidus mutants and rats treated with cortisol in early postnatal period. The development of the kidney sensitivity to AVP seems to be closely connected with the development of the molecular structure of the AVP receptor, age-related increase of the AVP-activated adenylate cyclase, and the maturation of cAMP-dependent protein kinases.
MeSH Terms
- Aging
- Animals
- Cytosol
- Diuresis
- Estradiol
- Hydrocortisone
- Kidney
- Kidney Concentrating Ability
- Male
- Mice
- Mice, Inbred CBA
- Protein Kinases
- Rats
- Rats, Inbred Strains
- Receptors, Angiotensin
- Receptors, Vasopressin
- Testosterone
- Vasopressins
Age-related changes in the regeneration of vasopressin (AVP) and oxytocin (OXT) axons after hypophysectomy in rats was immunohistochemically examined. Rats were hypophysectomized at 9, 16, 23, 30 and 90 days of age, and sacrificed 10 days after the operation. AVP or OXT immunoreactivity in the external layer of the median eminence (ME) was generally stronger in hypophysectomized immature rats than in hypophysectomized adult rats, and the age-related difference in immunoreactivity was more conspicuous for AVP axons than OXT ones. The cell body size of AVP or OXT neurons in hypophysectomized adult rats was not significantly different from the value of unoperated or initial control rats. However, the neurons in immature rats became significantly larger after hypophysectomy, compared with those of initial controls. These results indicate that AVP- and OXT-producing neurons in immature rats, as early as at 9 days of age, are endowed with the capacity of axonal rearrangement to the external layer of the ME after hypophysectomy, and that the stronger immunoreactivity in the external layer of the ME in immature rats than in the adult may be due to the differences in the rate of synthesis of neurohypophyseal hormones and the regenerative potency of neurons.
MeSH Terms
- Aging
- Animals
- Hypophysectomy
- Hypothalamo-Hypophyseal System
- Immunohistochemistry
- Male
- Median Eminence
- Nerve Regeneration
- Oxytocin
- RNA
- Rats
- Rats, Inbred Strains
- Supraoptic Nucleus
- Vasopressins
Age-related decreases have been reported in both vasopressinergic and cholinergic innervation in the rat brain. Since both systems are also sensitive to sex steroids, the effect of testosterone supplementation on vasopressin (AVP) levels and on choline acetyltransferase (ChAT) activity was investigated in the brains of young, middle-aged and aged male rats. Although no age-related changes in AVP levels were observed in the lateral septum or the medial amygdala (MA), peripheral testosterone administration raised AVP levels in the MA in all age groups. ChAT activity decreased with age in the medial preoptic area and was not restored by testosterone.
MeSH Terms
- Aging
- Animals
- Choline O-Acetyltransferase
- Frontal Lobe
- Male
- Preoptic Area
- Rats
- Testosterone
- Vasopressins
The number of neurons expressing vasopressin (AVP) was determined in the suprachiasmatic nucleus (SCN) of the hypothalamus of 41 human subjects ranging in age from 27 weeks of gestation up to 30 years of age. At term, i.e. at 38-42 weeks of gestation, the fetal SCN is still immature, since it then contains only about 13% of the adult number of AVP-expressing neurons. The period of rapid increase in the number of AVP-staining neurons in the SCN during the first few months postnatally coincides with the appearance of overt diurnal rhythms in the child.
MeSH Terms
- Adolescent
- Adult
- Aging
- Arginine Vasopressin
- Child
- Child, Preschool
- Female
- Gestational Age
- Humans
- Infant
- Infant, Newborn
- Male
- Suprachiasmatic Nucleus
Recently, the vasopressin (AVP) innervation in the rat brain was shown to be restored in senescent rats following long-term testosterone administration. In order to investigate whether this restoration is accompanied by an improvement in learning and memory, both sham- and testosterone-treated young (4.5 months), middle-aged (20 months), and aged (31 months) male Brown-Norway rats were tested in a Morris water maze. All animals learned to localize a cued platform equally well, indicating that the ability to learn this task was not affected by sensory, motoric, or motivational changes with aging or testosterone treatment. There were no significant differences in retention following cue training. Subsequent training with a hidden platform in the opposite quadrant of the pool (place training) revealed impaired spatial learning in middle-aged and aged animals. Retention following place training was significantly impaired in the sham-treated aged rats as compared with sham-treated young rats. Testosterone treatment did not improve spatial learning nor retention of spatial information, but, on the contrary, impaired retention in young and middle-aged animals. The present results confirm earlier reports on an impairment of spatial learning and memory in senescent rats but fail to support a role of decreased plasma testosterone levels and central AVP innervation in this respect.
MeSH Terms
- Aging
- Animals
- Brain
- Cues
- Discrimination Learning
- Escape Reaction
- Male
- Memory
- Mental Recall
- Orientation
- Rats
- Rats, Inbred BN
- Reaction Time
- Receptors, Angiotensin
- Receptors, Vasopressin
- Retention, Psychology
- Swimming
- Testosterone
This in vitro study examined the ontogeny of arginine vasopressin (AVP) and arginine vasotocin (AVT) compared with norepinephrine (NE)-mediated contraction in rat thoracic aortas. Aortas from three age groups (2-3 days, 6-7 days, and 12 wk) of Sprague-Dawley rats were used. Ring segment resting length was adjusted to optimize tension developed to a dose that produces half-maximal tension of NE in Krebs solution (pH 7.4, 37 degrees C) and gassed with 95% O2-5% CO2. Cumulative dose-response curves were generated for KCl (5-100 mM), NE (10(-10)-10(-5) M), AVP, and AVT (both 10(-10)-10(-6) M) in the presence and absence of a selective V1 vasopressinergic inhibitor, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin ([d(CH2)5Tyr(Me)]AVP). A progressive increase in sensitivity among all age groups was found for KCl and NE. There was a slight decrease in sensitivity to both AVP and AVT in the 1st wk. Maximum contractile response to NE increased between 2-3 and 6-7 days, whereas no change was observed for KCl, AVP, or AVT. AVP- and AVT-mediated contractions were selectively inhibited by [d(CH2)5Tyr(Me)]-AVP. These results suggest 1) receptor-mediated contractility is present from 2 days of age for NE, AVP, and AVT; 2) sensitivity to KCl and NE increases progressively during postnatal development, whereas sensitivity to AVP and AVT slightly decreases in the 1st wk with no progressive age-related increase by 12 wk; 3) AVP and AVT mediate contraction via a similar V1-like receptor.
MeSH Terms
- Aging
- Animals
- Aorta, Thoracic
- Arginine Vasopressin
- Female
- In Vitro Techniques
- Male
- Norepinephrine
- Pituitary Gland, Posterior
- Pituitary Hormones
- Potassium Chloride
- Rats
- Rats, Inbred Strains
- Vasoconstriction
- Vasopressins
- Vasotocin
Photoreceptor cell death after light-damage and during aging in rats is associated with the hormonal status of the animal, as well as other environmental and intrinsic factors. Restricted caloric intake extends the life of rodents and is usually accompanied by a reduction in water consumption. In this study, male and female rats were placed on restricted water intake for either 3 or 7 days to induce dehydration. Following exposure to damaging visible light, the retinas were evaluated for severity of damage and photoreceptor survival, heat shock (stress) protein (HSP) and total protein synthesis, and plasma arginine vasopressin (AVP) levels. Photoreceptor cells of 7-day, dehydrated male and female rats survived light-damage significantly better than those allowed water ad libitum; however, after 3 days of water restriction, only the male rats demonstrated protection from photodamage. Severity of photoreceptor damage could not be correlated with retinal HSP synthesis and content, although the latter was significantly reduced in dehydrated animals. Total retinal protein content and synthesis were unchanged by restricted water intake. AVP increased by 350% during the 7-day period of dehydration. Protection of photoreceptors from light-damage in this study may be correlated with osmotically stimulated changes in the retinas of dehydrated animals.
MeSH Terms
- Aging
- Animals
- Cell Survival
- DNA
- Electrophoresis, Gel, Two-Dimensional
- Female
- Light
- Male
- Photoreceptor Cells
- Proteins
- Rats
- Rats, Inbred Strains
- Retina
- Water Deprivation
Aging is known to reduce arginine vasopressin (AVP) response to volumetric stimulations and to increase AVP responses to osmotic stimuli and to administration of metoclopramide (MCP). In order to gain a better insight into the effect of age on AVP secretion, we evaluated AVP responses to cigarette smoking, MCP, and insulin-induced hypoglycemia in 30 male subjects aged 22-81 and divided into 3 groups by age. Basal AVP concentrations were similar in all groups. The AVP response during the insulin tolerance test had a similar pattern and magnitude (2.5-fold increase) in all groups. AVP responses to MCP and cigarette smoking were similar in the two younger groups, with plasma AVP levels increased 2 times by MCP and 2.5 times by cigarette smoking. In contrast, both MCP- and cigarette smoking-induced AVP rises were significantly higher in the oldest group, where plasma AVP concentrations increased 2.5 times after MCP and 3.25 times after smoking. When data of the MCP and cigarette smoking tests were combined, regression analyses showed a significant positive correlation between AVP peak responses to MCP and cigarette smoking in the oldest subjects. These data show that elderly humans have increased AVP responses not only to MCP but also to cigarette smoking, suggesting a common disorder for both alterations. In contrast, the lack of age-related changes in AVP response during the insulin tolerance test demonstrates that the mechanism underlying the AVP response to hypoglycemia is not affected by aging.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Arginine Vasopressin
- Blood Glucose
- Humans
- Hydrocortisone
- Hypoglycemia
- Insulin
- Male
- Metoclopramide
- Middle Aged
- Prolactin
- Smoking
- Time Factors
To determine whether aging influences arginine vasopressin (AVP) biosynthesis in the extrahypothalamic neurons of the bed nucleus of the stria terminalis (BNST), we used in situ hybridization and quantitative autoradiography to compare AVP mRNA in 3-month-old, 14-month-old, and 24-month-old male Fischer 344 rats. As AVP synthesis in the BNST has previously been shown to be steroid-dependent, plasma testosterone (T) was measured by radioimmunoassay. The 24-month-old animals had significantly fewer AVP-labelled cells than either the 3-month-old (p less than 0.01) or 14-month-old (p less than 0.05) animals. The cells that were present in the 24-month animals were less intensely labelled than in the other groups, as indicated by a significantly reduced number of grains per cell (p less than 0.01). Plasma T was also significantly lower in 24-month-old animals when compared with 3-month (p less than 0.01) or 14-month (p less than 0.05) groups. The results indicate that there is a marked age-related decline in vasopressin biosynthetic activity in neurons of the BNST.
MeSH Terms
- Aging
- Amygdala
- Animals
- Autoradiography
- Glycopeptides
- Histocytochemistry
- Male
- Nucleic Acid Hybridization
- Oligonucleotides
- RNA, Messenger
- Rats
- Rats, Inbred F344
- Testosterone
- Thalamic Nuclei
- Vasopressins
The experiments presented here have been designed to investigated whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studied the vagal control of the endocrine pancreas during food intake. Young (3 months old) and aged (27 months old) male Wistar rats were provided with permanent cardiac catheters allowing free movement and repeated, stress-free blood sampling. The vagally mediated preabsorptive insulin response (PIR) in relation to food intake as seen in young rats was reduced in aged ones. Blood glucose increments were the same at both ages. Administration of Amph (0.5 mg/kg; s.c.) 30 min before, or AVP (10 micrograms/kg; s.c.) 60 min before presentation of a test meal led to an elevation of the magnitude of insulin secretion in young rats but reduced the response in aged rats. Moreover, the PIR was not reinstated in aged rats. Blood glucose increments were not influenced by the treatments. The results are interpreted in terms of age-related general reduction of parasympathetic reactivity. The differential effect of amphetamine and AVP treatment on the insulin response suggests that the central aminergic or peptidergic drive of vagal output to the endocrine pancreas is also age-related.
MeSH Terms
- Aging
- Amphetamine
- Analysis of Variance
- Animals
- Arginine Vasopressin
- Blood Glucose
- Eating
- Insulin
- Insulin Secretion
- Male
- Rats
- Rats, Inbred Strains
In this study, we investigated age-associated changes in neuroaxonal transport of the hormone vasopressin (AVP) and its associated neurophysin (NPII), from the supraoptic nucleus (SON) of the hypothalamus to the neurohypophysis. C57BL/Icrfat male mice of 6 and 28 months of age were injected in the hypothalamus with L-[35S]cysteine. Animals were killed up to 2.25 h after injection and NPII and AVP from the SON and neurohypophysis were separated using HPLC, and the fractions counted for radioactivity. In the SON, radiolabelled NPII and AVP were first detected after 0.50 h in both young and old mice. There was no significant difference between the age-groups in the incorporation of radiolabel over the time course studied. Radiolabelled NPII in the neurohypophysis was significantly above background after 1.25 h in the young, and after 1.50 h in the old mice. The differences between the two age groups was significant (P = 0.05). Radiolabelled AVP followed a similar trend, but was not significantly above background until 1.50 h in the young and 1.75 h in the old. The differences between the two age groups was on the point of significance (P = 0.056). These results indicate a significant reduction of up to 25% in the rate of axonal transport of neurohypophyseal peptides with advancing age.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Axons
- Hypothalamo-Hypophyseal System
- Male
- Mice
- Mice, Inbred C57BL
- Neurons
- Neurophysins
- Pituitary Gland, Posterior
- Supraoptic Nucleus
The effects of chronic ethanol feeding on norepinephrine (NE)- and arginine-vasopressin (AVP)-stimulated phosphoinositide (PI) hydrolysis in rat liver slices was determined. The maximum NE-stimulated PI response was significantly reduced by 40% in liver slices from 8-month-old rats which had been treated for 5 months with a liquid diet containing ethanol compared to pair-fed controls. The maximum AVP-stimulated PI response was decreased by 39% in liver slices from the ethanol-fed rats compared to control. EC50 values for NE- and AVP-stimulated PI hydrolysis in liver slices were not affected by the chronic ethanol treatment. Similar reductions in the maximal NE- and AVP-stimulated PI hydrolysis (28% and 27%, respectively) were found in 22-month-old rats which had been maintained on an ethanol containing diet for 5 months compared to pair-fed controls. The binding of [3H]prazosin and [3H]AVP to liver plasma membranes from 8-month-old ethanol-fed rats was not significantly different from binding to liver membranes from sucrose-fed controls. Our data suggest that chronic ethanol ingestion may lead to a reduction in PI-linked signal transduction in liver.
MeSH Terms
- Aging
- Alcoholism
- Animals
- Arginine Vasopressin
- Hydrolysis
- In Vitro Techniques
- Liver
- Male
- Norepinephrine
- Phosphatidylinositols
- Prazosin
- Radioligand Assay
- Rats
- Rats, Inbred F344
- Receptors, Cell Surface
- Tritium
The relationship between arginine vasopressin (AVP) secretion and the age-related change in renal concentrating ability was studied in 10-, 20-, and 30-mo-old conscious rats. In control condition, urine osmolality (Uosmol) was 2,358 /- 99, 1,919 /- 87, and 1,135 /- 173 mosmol/kgH2O (mean /- SE) and the corresponding plasma AVP concentration 3.1 /- 1.2, 2.8 /- 0.7, and 3.3 /- 0.7 pg/ml at 10, 20, and 30 mo. Urinary AVP excretion and AVP content in the hypothalamus were comparable in the 3 age groups, while the basal AVP pituitary content was significantly higher at 10 than at 20 or 30 mo. Three days of dehydration induced 1) a similar increase in plasma concentration and urinary excretion of AVP in the 3 groups, even though the maximal Uosmol reached by the oldest animals was significantly reduced (3,988 /- 218, 3,652 /- 273, and 2,826 /- 197 mosmol/kgH2O at 10, 20, and 30 mo, respectively) and 2) a similar AVP depletion of the pituitary at 10, 20, and 30 mo and an increase of the AVP content in the hypothalamus at 10 mo but not at 20 and 30 mo. These results suggest that the decrease in renal concentrating ability reported in aging rats is not due to an inappropriate secretion of AVP along the hypothalamo-neurohypophysial axis but is rather related to an impaired responsiveness of the kidney to the antidiuretic hormone.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Blood
- Brain
- Dehydration
- Diuresis
- Female
- Kidney Concentrating Ability
- Osmolar Concentration
- Radioimmunoassay
- Rats
- Rats, Inbred Strains
- Tissue Distribution
The influence of age on several parameters related to water balance was studied in Wistar rats. Plasma AVP concentration and plasma osmolality were increased at midday in 21-month-old rats as compared with 3- and 4-month-old rats. Daily water intake per 100 g body weight was reduced in 14- and 21-month-old rats as compared with 3- and 4-month-old rats, but total water intake was unaltered. These results suggest that there is a change in water balance in Wistar rats with age. In order to obtain information about the influence of age on daily fluctuations in plasma AVP concentration and osmolality these parameters were determined in 4-month-old Wistar rats sacrificed at 2 h intervals during the day and in 20- and 31-month-old rats sacrificed at 8 h intervals. Plasma AVP concentrations were low during the light period and high during the dark period in 4-month-old rats. The relationship between plasma osmolality and plasma AVP concentration was dependent on the time of day in 4-month-old-rats. Plasma AVP concentrations were higher at 16.00 than at 08.00 and 24.00 in 20-month-old rats, and higher at 24.00 than at 08.00 and 16.00 in 31-month-old rats. In contrast to the plasma AVP concentration during the light period, the average daily AVP concentration (average of plasma AVP concentrations at 08.00, 16.00 and 24.00) was increased in 31-month-old rats only. The relationship between plasma osmolality and plasma AVP concentration was not age-related.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Circadian Rhythm
- Male
- Osmolar Concentration
- Rats
- Rats, Inbred Strains
Aging is associated with a decline in renal concentrating ability in response to dehydration-induced arginine vasopressin (AVP) release. To examine target tissue sensitivity, cortical collecting tubules (CCT) were individually microdissected from young (3 months), middle-aged (2-3 years) and old (4-5.5 years) rabbits and subjected to in vitro perfusion analysis and tissue culture of defined epithelial monolayers. Osmotic fluid transport was compared with adenylate cyclase activity and an age-associated decline in both parameters detected in response to increasing doses of AVP. [3H]-AVP binding was unchanged in CCT epithelia of different ages, excluding receptor alterations as the underlying mechanism. Also, hydraulic conductivity measurements of isolated young and old CCT were not significantly different, excluding post-cAMP events as a major mechanism of reduced sensitivity. Effects of cholera toxin and forskolin on hydraulic conductivity and adenylate cyclase activity showed a dramatic decrease in the ability of these compounds to elicit a response in CCT epithelia from old rabbits. It was concluded that alterations in Gs proteins and the catalytic unit of adenylate cyclase-were responsible for the age-associated decline in CCT response to AVP.
MeSH Terms
- Adenylyl Cyclases
- Aging
- Animals
- Biological Transport, Active
- GTP-Binding Proteins
- In Vitro Techniques
- Kidney
- Kidney Concentrating Ability
- Kidney Tubules, Collecting
- Perfusion
- Rabbits
- Water
In young male Wistar rats sudden silence superimposed on low intensity background noise evokes a relative decrease in heart rate. This bradycardia is accompanied by immobility behavior. In the present study, involving young (3 month), late-adult (14 month), aged (20 month), and senescent (25 month) rats the magnitude of the stress-induced bradycardia shows an age-related reduction while the behavioral immobility response remained unchanged during the process of aging. Arginine-8-vasopressin (AVP, 6 micrograms/kg SC) administered 60 min prior to the experiment led to a prolonged behavioral and cardiac stress response in young and late-adult rats, but not in aged and senescent animals. The peripheral and central mechanisms possibly involved in the failure of systemically applied AVP to improve bradycardiac stress responses in aged rats are discussed.
MeSH Terms
- Aging
- Animals
- Arginine Vasopressin
- Arousal
- Electrocardiography
- Heart
- Heart Rate
- Injections, Subcutaneous
- Male
- Motor Activity
- Nerve Net
- Parasympathetic Nervous System
- Rats
- Rats, Wistar
- Signal Processing, Computer-Assisted
Many changes in the neuroendocrine axis occur with healthy normal aging in humans. Women cease ovarian follicle maturation and menstrual cycles entering the estrogen-deficient state termed menopause. Although not without risk, estrogen and progesterone replacement in postmenopausal women has been shown to ameliorate the complications of lowered estradiol concentrations, such as hot flushes and osteoporsis, while improving the risk of cardiovascular complications. Aging men have lowered serum free and total testosterone concentrations and may experience a less well defined symptom complex termed andropause. Both signs and symptoms of thyroid disease and interpretation of thyroid function tests are difficult in aging humans. Specifically, TSH secretion is diminished in aging so that suppressed serum TSH concentrations are indicative of but not specific for hyperthyroidism. Cortisol secretion is not altered in aging, although serum concentrations of DHEA-S are lower. Prolactin concentrations are increased in both men and women, with the increase being more pronounced in men. The clinical significance of this increase has not yet been determined. Finally, elderly humans are more likely to develop difficulties with fluid and electrolyte balance. Although some alterations in AVP secretion have been shown in the elderly, plasma concentrations are similar in young and elderly subjects. Other mechanisms, such as decreased glomerular filtration rate and a decreased sensitivity of the thirst mechanism in response to hypertonicity, may be important contributors to fluid and electrolyte imbalances.
MeSH Terms
- Aging
- Estrogen Replacement Therapy
- Estrogens
- Female
- Humans
- Male
- Menopause
- Neurosecretory Systems
- Pituitary Gland
- Pituitary Hormones
- Progestins
- Thyroid Gland
The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH Terms
- Adult
- Aging
- Arginine Vasopressin
- Atrial Natriuretic Factor
- Bicycling
- Catecholamines
- Cold Temperature
- Exercise
- Hematocrit
- Hemoglobins
- Hormones
- Humans
- Lactates
- Lactic Acid
- Male
- Middle Aged
- Oxygen Consumption
- Plasma Volume
- Potassium
- Renin
- Sodium
We previously reported that insulin-induced hypoglycemia (IIH) induces a large increase in plasma ACTH and corticosterone levels in the developing rat during the stress hyporesponsive period and that this effect is mediated, at least partially, by arginine vasopressin (AVP), but not corticotropin-releasing factor. Nevertheless, ACTH secretion in response to IIH in rats immunoneutralized against AVP was still stimulated, suggesting that other regulatory factors participate in the stimulation of ACTH secretion during IIH. It has been suggested that, in the adult rat, during profound hypoglycemia, epinephrine may act at the pituitary level through beta 2-adrenergic receptors to stimulate ACTH secretion. In this report, we studied the effect of the blockade of beta-adrenergic receptors on the pituitary-adrenal axis response to IIH. Rats (20 or 8 day old) were pretreated with saline or 2.5 mg/kg propranolol (a beta-adrenergic receptors antagonist) and subsequently injected with 3 IU/kg insulin. In 20-day-old rats, insulin injection induced a large increase of plasma ACTH concentrations that were unaffected by propranolol pretreatment. In 8-day-old rats, the IIH-induced increase of plasma ACTH levels was significantly reduced by propranolol pretreatment. Pretreatment of 8-day-old rats with 5 mg/kg CGP 20712A (a selective beta 1-adrenergic receptor antagonist) did not change the plasma ACTH response to insulin injection, while pretreatment with 2.5 mg/kg ICI 118551 (a selective beta 2-adrenergic receptor antagonist) resulted in a significant decrease of the IIH-induced stimulation of ACTH secretion. We next studied the effect of the blockade of circulating AVP and/or beta-adrenergic receptors on the pituitary response to IIH. Pretreatment of 8-day-old rats with antiserum anti-AVP or propranolol was followed by a significant reduction of IIH-induced increase of plasma ACTH concentrations. No additive effect was found after pretreatment with both antiserum anti-AVP and propranolol, suggesting that the stimulatory effect of catecholamines during IIH in 8-day-old rats is mediated through a modulation of hypothalamic AVP secretion.
MeSH Terms
- Adrenergic beta-Antagonists
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Catecholamines
- Hypoglycemia
- Imidazoles
- Immunization, Passive
- Insulin
- Propanolamines
- Propranolol
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, beta
In the neonatal rat, the response of the hypothalamo-pituitary-adrenal axis to stressful stimuli is markedly decreased during the first 2 weeks of life. This peculiar period was named "stress hyporesponsive period." In this report, we studied the effect of insulin-induced hypoglycemia, known as a strong stimulator of the corticotroph function in the adult rat. Rats (8- or 20-day-old) were injected ip with 3 IU/kg synthetic insulin and were killed at various times. In 20-day-old rats, hypoglycemia induced a rapid drop in blood glucose concentrations accompanied by a stimulation of ACTH and corticosterone secretion which reached maximal values within 30 min. On the opposite, in 8-day-old rats, despite a rapid decrease in blood glucose levels, insulin injection induced a gradual rise of plasma ACTH and corticosterone concentrations which peaked at 90 min. This delayed response of the hypothalamo-pituitary-adrenal axis to hypoglycemia in the youngest rats does not seem to be due to a difference of sensitivity to insulin-induced hypoglycemia since injection of increasing doses of insulin (0.3, 0.75, or 3 IU/kg body wt) induced a dose-related decrease of blood glucose concentrations and a rise in plasma ACTH and corticosterone levels, comparable in the two age group studied. Basal or hypoglycemia-stimulated absolute corticosterone values were much lower in 8-day-old rats than in 20-day-old animals, suggesting an immaturity of the adrenal glands in the youngest animals. Daily ACTH injection, starting 3 days before the experiment, had a trophic effect on the adrenal glands leading to a more important increase of corticosterone levels after hypoglycemia in 8-day-old rats. Our results confirm that there is an immaturity of the adrenal glands in young rats, probably due to the low plasma ACTH levels during the neonatal period. To determine the respective role of the two major hypothalamic ACTH secretagogues, we studied the effect of passive immunization against CRF or arginine vasopressin (AVP) on plasma ACTH response after hypoglycemia. Passive immunization against AVP decreased significantly hypoglycemia-stimulated ACTH secretion in both 8- and 20-day-old rats, while no change of plasma ACTH response to insulin injection was observed after passive immunization against CRF. This results suggest that CRF does not seem to be involved in the regulation of ACTH secretion after hypoglycemia in the young rat while AVP seems to be the main hypothalamic stimulatory factor for anterior pituitary corticotrophs response to hypoglycemia during the postnatal period.(ABSTRACT TRUNCATED AT 400 WORDS)
MeSH Terms
- Adrenal Glands
- Adrenocorticotropic Hormone
- Aging
- Animals
- Arginine Vasopressin
- Blood Glucose
- Corticosterone
- Corticotropin-Releasing Hormone
- Hyperglycemia
- Immunization, Passive
- Insulin
- Kinetics
- Rats
- Rats, Inbred Strains
- Recombinant Proteins
- Reference Values
- Time Factors
The effect of age on the hypothalamic-hypophyseal-renal axis in normal man was determined by assaying plasma arginine vasopressin (AVP) responses to inhibitory and to secretory stimuli. Nine young (21-49 years) and 13 old (54-92 years) subjects received IV ethanol (375 mg/m2 per min). AVP levels fell progressively during the infusion in the young group, but fell for only 30 min in the old group and then rose paradoxically despite the continuing increase in blood ethanol. Eight young (22-48 years) and 8 old (52-66 years) men were provided identical osmolal loads by a 2-hour IV infusion of 3% NaCl at 0.1 ml/kg per min. Serum AVP rose 2.5 times the baseline in the young and 4.5 times the baseline in the old men despite identical free water clearances. Osmoreceptor sensitivity (the slope of AVP on osmolality) was greater in the old subjects. The heightened sensitivity to hyperosomolality helps examine the paradoxical response to ethanol, since osmolality increased during that time. This increased AVP response may severe to compensate for the reduced renal ability to conserve salt and water in aging man.
MeSH Terms
- Adult
- Aging
- Arginine Vasopressin
- Depression, Chemical
- Ethanol
- Humans
- Hypothalamo-Hypophyseal System
- Kidney
- Male
- Middle Aged
- Osmolar Concentration
- Saline Solution, Hypertonic
- Secretory Rate
- Sodium Chloride
- Stimulation, Chemical
- Vasopressins