Peripheral Arginine Vasopressin Research Articles

FRI004 Sex Differences In Oxytocin And Arginine-Vasopressin Levels Around A Standardized Meal In Adults With Obesity

Abstract Disclosure: M. Wronski: None. J.T. Sanislow: None. K. Holman: None. J. Gydus: None. M. Muhammed: None. S. Smith: None. E. Asanza: None. E.R. Golden: None. N. Hadaway: None. S. Ehrlich: None. A. Aulinas Maso: None. L. Kerem: None. J.M. Davis: None. H.P. Nazarloo: None. S. Carter: None. F. Plessow: None. E.A. Lawson: None. Objective: Oxytocin (OXT) and arginine-vasopressin (AVP) are neurohormones involved in metabolism that are regulated by gonadal steroid levels. OXT tends to be higher in healthy-weight females than males; levels decrease following a meal with an associated reduction in appetite. In contrast, AVP tends to be lower in healthy-weight females than males; post-prandial AVP response has not been examined. OXT and AVP levels in response to feeding and the impact of sex are important to study in individuals with obesity to improve our understanding of disease pathophysiology and advance treatment. We investigated peripheral OXT and AVP levels in female and male adults with obesity fasting and at three post-prandial time points (TP). Methods: The diverse study sample of 56 non-diabetic adults with obesity (35.71% non-White, 19.64% Hispanic) included 30 premenopausal females and 26 males (age: mean ± SEM = 33.73 ± 0.83 years, range = 18.60 - 45.71 years; BMI: 36.77 ± 0.66 kg/m2, 30.20 - 50.60 kg/m2). We tested sex differences in age and BMI using two-samples t-tests. Plasma samples were collected fasting and 30, 60, and 120 minutes (TP) after a standardized ∼500 kcal meal to measure OXT and AVP levels (using enzyme-linked immunosorbent assays). OXT and AVP levels deviating >3*SD from the hormone-, sex-, and TP-specific mean were excluded prior to log-transformation to approximate normality. Sex differences and meal-related dynamics in OXT and AVP levels were examined using two random-intercept linear mixed effects models with predictors sex, TP, and sex-x-TP interaction, covarying for BMI (false discovery rate across both models). Results: Age and BMI did not differ between sexes (ps ≥ 0.354). Across TPs, female sex significantly predicted lower OXT (F(1,53) = 4.90, FDR-q = 0.031, partial eta squared = 0.08, adjusted mean ± SEM females = 273.95 ± 1.12 pg/mL versus males = 397.61 ± 1.13 pg/mL) and lower AVP (F(1,52) = 5.04, FDR-q = 0.031, partial eta squared = 0.09, adjusted mean ± SEM females = 79.77 ± 1.21 pg/mL versus males = 149.39 ± 1.22 pg/mL). TP and sex-x-TP interaction effects were nonsignificant. Conclusion: In this first study to investigate sex differences and meal-dependent changes in OXT and AVP levels in adults with obesity, we found that levels of both neurohormones were lower in females than males. In contrast to our previous finding of a post-prandial decrease in OXT, associated with change in appetite in healthy-weight females, there was no impact of food intake on OXT or AVP levels in adults with obesity. Our data indicate that in obesity, OXT and AVP levels are sexually dimorphic and postprandial dynamics may be dysregulated. Presentation: Friday, June 16, 2023

Contrasting central and systemic effects of arginine-vasopressin on urinary marking behavior as a social signal in male mice

Arginine-vasopressin (AVP) is a neurohypophyseal peptide that plays a critical role in the regulation of social behavior in mammals. Neuronal AVP regulates male-specific social signaling processes, such as exocrine urinary scent deposition and marking behavior in mice. In the periphery, AVP is transported to the portal bloodstream and acts as an antidiuretic hormone. These AVP dynamics imply that the central role of AVP in the stimulation of urinary marking is dissociated with the peripheral role of AVP in the retention of osmotic conditions. Using male BALB/c mice as subjects, peripheral injection of AVP decreased urinary marking and urination. In contrast, a central infusion of AVP facilitated urinary marking with no effect on urination, while an antagonist of the AVP 1a receptor inhibited marking. Centrally AVP-injected mice also exhibited typical behaviors, such as hiccough/sneeze-like reactions and flash scratching, particularly when confronted with a stimulus mouse through a wire mesh screen. Significant expression of these typical reactions in these mice resulted in the disruption of marking deposition. Further analysis of AVP synthesis illustrated that AVP levels increased in the midbrain but not in the circulation immediately after the test, particularly when confronted with a stimulus mouse. The central AVP regulates urinary marking and other typical behaviors in a dose- and situation-dependent manner. The sequential process implies that centrally synthesized AVP may be secreted into the circulation following immediate neuronal processes, and then peripheral AVP acts as an antidiuretic hormone on urinary marking behavior.

Surge of Peripheral Arginine Vasopressin in a Rat Model of Birth Asphyxia.

Mammalian birth is accompanied by a period of obligatory asphyxia, which consists of hypoxia (drop in blood O2 levels) and hypercapnia (elevation of blood CO2 levels). Prolonged, complicated birth can extend the asphyxic period, leading to a pathophysiological situation, and in humans, to the diagnosis of clinical birth asphyxia, the main cause of hypoxic-ischemic encephalopathy (HIE). The neuroendocrine component of birth asphyxia, in particular the increase in circulating levels of arginine vasopressin (AVP), has been extensively studied in humans. Here we show for the first time that normal rat birth is also accompanied by an AVP surge, and that the fetal AVP surge is further enhanced in a model of birth asphyxia, based on exposing 6-day old rat pups to a gas mixture containing 4% O2 and 20% CO2 for 45 min. Instead of AVP, which is highly unstable with a short plasma half-life, we measured the levels of copeptin, the C-terminal part of prepro-AVP that is biochemically much more stable. In our animal model, the bulk of AVP/copeptin release occurred at the beginning of asphyxia (mean 7.8 nM after 15 min of asphyxia), but some release was still ongoing even 90 min after the end of the 45 min experimental asphyxia (mean 1.2 nM). Notably, the highest copeptin levels were measured after hypoxia alone (mean 14.1 nM at 45 min), whereas copeptin levels were low during hypercapnia alone (mean 2.7 nM at 45 min), indicating that the hypoxia component of asphyxia is responsible for the increase in AVP/copeptin release. Alternating the O2 level between 5 and 9% (CO2 at 20%) with 5 min intervals to mimic intermittent asphyxia during prolonged labor resulted in a slower but quantitatively similar rise in copeptin (peak of 8.3 nM at 30 min). Finally, we demonstrate that our rat model satisfies the standard acid-base criteria for birth asphyxia diagnosis, namely a drop in blood pH below 7.0 and the formation of a negative base excess exceeding −11.2 mmol/l. The mechanistic insights from our work validate the use of the present rodent model in preclinical work on birth asphyxia.

Salivary Oxytocin and Vasopressin Levels in Police Officers With and Without Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is characterised by symptoms associated with maladaptive fear and stress responses, as well as with social detachment. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) have been associated with both regulating fear and neuroendocrine stress responsiveness and social behaviour. However, there is only limited evidence for dysregulated peripheral OT and AVP levels in PTSD patients. The present study aimed to investigate basal salivary OT and AVP levels in trauma-exposed male and female police officers with and without PTSD. Saliva samples were collected during rest and OT and AVP levels were determined using a radioimmunoassay. Men and women were analysed separately, having adjusted for differences in trauma history, and for hormonal contraception use in women. The results showed that male PTSD patients had lower basal salivary OT levels, and did not differ in AVP levels compared to male trauma-exposed healthy controls after adjusting for childhood emotional abuse. There were no significant differences in basal salivary OT and AVP levels in women. Our findings indicate potential dysfunctioning of the OT system in male PTSD patients. Future studies are needed to replicate these findings and to further unravel the relationship between the OT and AVP systems, sex, trauma history and PTSD.

The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human

It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5±2.5pg/ml), not plasma (13.2±4.2pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1±3.8pg/ml and 12.3±3.4pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral “Zusanli” points (St. 36) for 60min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients.

Arginine vasopressin plasma levels change seasonally in African striped mice but do not differ between alternative reproductive tactics

Arginine vasopressin (AVP) is an important hormone for osmoregulation, while as a neuropeptide in the brain it plays an important role in the regulation of social behaviors. Dry habitats are often the home of obligately sociable species such as meerkats and Damaraland mole-rats, leading to the hypothesis that high plasma AVP levels needed for osmoregulation might be associated with the regulation of social behavior. We tested this in a facultative sociable species, the African striped mouse (Rhabdomys pumilio). During the moist breeding season, both solitary- and group-living reproductive tactics occur in this species, which is obligatory sociable in the dry season. We collected 196 plasma samples from striped mice following different reproductive tactics both during the moist and the dry season. Solitary mice did not have lower AVP levels than sociable mice, rejecting the hypothesis that peripheral AVP is involved in the regulation of alternative reproductive tactics. However, we found significantly higher AVP levels during the dry season, with AVP levels correlated with the abundance of food plants, the main source of water for striped mice. Plasma AVP levels were not correlated with testosterone or corticosterone levels. Our study underlines the important role that AVP plays in osmoregulation, particularly for a free ranging mammal living under harsh arid conditions.

Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain

Defining how arginine vasopressin (AVP) acts centrally to regulate homeostasis and behavior is problematic, as AVP is made in multiple nuclei in the hypothalamus (i.e., paraventricular [PVN], supraoptic [SON], and suprachiasmatic [SCN]) and extended amygdala (i.e., bed nucleus of the stria terminalis [BNST] and medial amygdala [MeA]), and these groups of neurons have extensive projections throughout the brain. To understand the function of AVP, it is essential to know the site of origin of various projections. In mice, we used gonadectomy to eliminate gonadal steroid hormone-dependent expression of AVP in the BNST and MeA and electrolytic lesions to eliminate the SCN, effectively eliminating those AVP-immunoreactive projections; we also quantified AVP-immunoreactive fiber density in gonadectomized and sham-operated male and female mice to examine sex differences in AVP innervation. Our results suggest that the BNST/MeA AVP system innervates regions containing major modulatory neurotransmitters (e.g., serotonin and dopamine) and thus may be involved in regulating behavioral state. Furthermore, this system may be biased toward the regulation of male behavior, given the numerous regions in which males have a denser AVP-immunoreactive innervation than females. AVP from the SCN is found in regions important for the regulation of hormone output and behavior. Innervation from the PVN and SON is found in brain regions that likely work in concert with the well-known peripheral AVP actions of controlling homeostasis and stress response; female-biased sex differences in this system may be related to the heightened stress response observed in females.

Arginine vasopressin does not mediate heat loss in the tail of the rat

It has been reported that hypothermia induced by arginine vasopressin (AVP) is brought about by a coordinated response of reduced thermogenesis in brown adipose tissue (BAT) and increased heat loss through the tail of rats. However, it is well known that AVP is one of the strongest peripheral vasoconstrictors. Whether the AVP-induced hypothermia is associated with an increase in heat loss through the tail is questionable. Therefore, the present study assessed the relationship between the effects of AVP on tail skin temperature and the induced hypothermic response, and to determine if peripheral AVP administration increases heat loss from the tail. Core, BAT and tail skin temperature were monitored by telemetry in male Sprague–Dawley rats before and after intraperitoneal administration of AVP or vasopressin receptor antagonist. We also analyzed simultaneously of the time-course of AVP-induced hypothermic response and its relationship with changes in BAT temperature, and effect of AVP on grooming behavior. The key observations in this study were: (1) rats dosed with AVP induced a decrease in heat production (i.e., a reduction of BAT thermogenesis) and an increase of saliva spreading for evaporative heat loss (i.e., grooming behavior); (2) AVP caused a marked decrease in tail skin temperature and this effect was prevented by the peripheral administration of the vasopressin V1a receptor antagonist, suggesting that exogenous AVP does not increase heat loss in the tail of rats; (3) the vasopressin V1a receptor antagonist could elevate core temperature without affecting tail skin temperature, suggesting that endogenous AVP is involved in suppression of thermogenesis, but not mediates heat loss in the tail of rats. Overall, the present study does not support the conclusion of previous reports that AVP increased tail heat loss in rats, because AVP-induced hypothermia in the rat is accompanied by a decrease in tail skin temperature. The data indicate that exogenous AVP-induced hypothermia attributed to the suppression of thermoregulatory heat production and the increase of saliva spreading for evaporative heat loss.

Central Endogenous Vasopressin Induced by Central Salt‐Loading Participates in Body Fluid Homeostasis through Modulatory Effects on Neurones of the Paraventricular Nucleus in Conscious Rats

Peripherally secreted arginine vasopressin (AVP) plays a role in controlling body fluid homeostasis, and central endogenous AVP acts as a neurotransmitter or neuromodulator. The limbic system, which appears to exert an inhibitory effect on the endocrine hypothalamus, is also innervated by fibres that contain AVP. We examined whether central endogenous AVP is also involved in the control of body fluid homeostasis. To explore this possibility, we examined neuronal activity in the paraventricular nucleus of the hypothalamus (PVN), periventricular parts of the PVN and limbic brain areas, as well as AVP mRNA expression in the PVN and the peripheral secretion of AVP after central salt-loading in rats that had been pretreated i.c.v. with the AVP V(1) receptor antagonist OPC-21268. Neuronal activity in the PVN evaluated in terms of Fos-like immunoreactivity (FLI), especially in the parvocellular subdivisions, was suppressed. On the other hand, FLI was enhanced in the lateral septum, the bed nucleus of the stria terminalis and the anterior hypothalamic area. Similarly, AVP mRNA expression was enhanced in the magnocellular subnucleus of the PVN, despite the lack of a significant difference in the peripheral AVP level between OPC-21268- and vehicle-pretreated groups. We recorded renal sympathetic nerve activity (RSNA) as sympathetic nerve outflow during central salt-loading. The suppression of RSNA was significantly attenuated by i.c.v. pretreatment with OPC-21268. These results suggest that the suppression of RSNA during central salt-loading might be the result of a decrease in neuronal activity in the parvocellular subdivisions of the PVN via the inhibitory action of central endogenous AVP. The parvocellular and magnocellular neurones in the PVN might show different responses to central salt-loading to maintain body fluid homeostasis as a result of the modulatory role of central endogenous AVP.

Arginine vasopressin and adrenocorticotropin secretion in response to psychosocial stress is attenuated by ethanol in sons of alcohol-dependent fathers

Familial risk and environmental stress promote the development of alcohol dependence. We investigated whether a positive family history of alcoholism affects the neuroendocrine response to a standardized laboratory stress test in healthy subjects without alcohol use disorders. Twenty-four high-risk subjects with a paternal history of alcoholism (PHA) and 16 family history negative (FHN) controls were evaluated. Psychosocial stress was induced by having subjects deliver a 5-min speech and mental arithmetics in front of an audience on separate days, after drinking either placebo or ethanol (0.6 g/kg) in a randomized sequence. Adrenocorticotropin (ACTH) was measured in 10 plasma samples covering up to 75 min after the stress test. Plasma arginine vasopressin (AVP) was determined before the stressor, at the time of maximum ACTH secretion, and at 75 min after stress onset. The stress test induced a phasic increase in ACTH secretion. At the time of maximum ACTH, AVP was significantly increased in relation to baseline. Compared to placebo, alcohol administration significantly attenuated maximum ACTH concentration in PHA but not FHN subjects, and decreased AVP measured in the same samples in PHA but not FHN subjects. We conclude that activation of the hypothalamic–pituitary–adrenal system by psychosocial stress is accompanied by an increase in peripheral plasma AVP levels. Secretion of both ACTH and AVP suggest that alcohol attenuates the stress response selectively in PHA but not FHN subjects. This might imply some short-term positive alcohol effect in sons of alcoholics, but also constitute a mechanism by which their risk to develop alcohol use disorders is increased.

Changes of central norepinephrine, beta-endorphin, LEU-enkephalin, peripheral arginine-vasopressin, and angiotensin II levels in acute and chronic phases of sino-aortic denervation in rats.

We and others have demonstrated that impaired arterial baroreceptor reflex (ABR) function is one of the major causes of hypertension-associated end organ damage. The goal of this study was to clarify the potential neuro-humoral mechanisms responsible for impaired ABR-induced end organ damage. The sino-aortic denervated (SAD) rat was used as an animal model of ABR dysfunction. One-week SAD rats were characterized by hypertension, tachycardia, increased norepinephrine content, and decreased beta-endorphin and leu-enkephalin content in hypothalamus and medulla oblongata, and increased plasma levels of arginine-vasopressin. In 18-week SAD rats, the 24-hour average arterial pressure, heart rate, beta-endorphin, and leu-enkephalin content in hypothalamus and medulla oblongata and plasma levels of arginine-vasopressin and angiotensin II were not different from those measured in ABR-intact rats. However, blood pressure variability and angiotensin II content in kidney and left ventricle increased. When exposed to chronic stress, exaggerated changes in arterial pressure, blood pressure variability, the levels of central norepinephrine, beta-endorphin and leu-enkephalin, plasma arginine-vasopressin and angiotensin II, and tissue angiotensin II were found in 18-week SAD rats. These data indicate that a long-term impairment of ABR leads to chronic activation of central noradrenergic neurons and tissue renin-angiotensin system, and that stress induces exaggerated responses of neuro-humoral factors and hemodynamics in SAD rats. Thus, if the present results hold true for humans, one can expect abnormal neurotransmitter/neuromodulator responses to environmental insults in patients with impaired ABR function.

The Effects of Peptides on Partner Preference Formation Are Predicted by Habitat in Prairie Voles

This study tested the hypothesis that intraspecific variations in mating systems are correlated with differences in the capacity of peripheral arginine vasopressin (AVP) to facilitate partner preferences. It has been hypothesized that differences in environmental conditions, Kansas being more xeric than Illinois, are responsible for some of the intraspecific differences in the mating systems between Kansas (KN) and Illinois (IL) prairie voles. We predicted that prairie voles from KN would be more behaviorally sensitive to peripheral AVP than prairie voles from IL. To test this hypothesis 60- to 120-day-old male and female, lab-reared, prairie voles originating from KN and IL received three subcutaneous injections of AVP or isotonic saline. Animals were then placed with an adult member of the opposite sex, designated a “partner,” for a 1-hour period of cohabitation and subsequently tested for preference for the familiar partner versus a comparable stranger. Only KN males treated with AVP displayed a significant preference for the partner. Using the same experimental paradigm we also examined the ability of peripheral oxytocin (OT) to facilitate partner preference in KN prairie voles. OT facilitated partner preference in females, but not males. This finding was consistent with previous results describing the effects of peripheral OT in IL prairie voles. We also examined the hypothesis that the differential response of KN and IL males would be associated with differences in the distribution of AVP (V1a) receptors. However, there was no apparent difference in the distribution of V1a receptors between KN and IL males. The results of this study indicate that there is both intraspecific and intersexual variation in the regulation of social behavior in prairie voles. In addition, these findings suggest that the proximate causes of intraspecific variation may be predicted by knowledge of the habitat of origin.

Participation of arterial baroreceptors input and peripheral vasopressin in the suppression of renal sympathetic nerve activity induced by central salt loading in conscious rats

We examined whether renal sympathetic nerve activity (RSNA) is suppressed in response to intracerebroventricular (i.c.v.) administration of hypertonic saline (HS) in conscious rats. RSNA was suppressed by i.c.v. administration of HS (0.3 M, 0.67 M, and 1.0 M, 1 μl/min for 20 min) in a concentration-dependent manner, which was attenuated under pentobarbital anesthesia. To elucidate mechanisms responsible for central HS-induced decrease in RSNA, possible involvement of arterial baroreceptors and peripheral arginine vasopressin (AVP) secreted from the posterior pituitary gland was examined using sinoaortic denervated (SAD) rats and non-peptide vasopressin receptor antagonists. The maximum suppression of RSNA (−81.5±5.5%) in control rats was significantly attenuated to −32.5±6.7% in SAD rats and to −55.8±5.7% in rats pretreated with intravenous vasopressin V 1 receptor antagonist, OPC-21268 (5 mg/kg, i.v.). However, in SAD rats, pretreatment with vasopressin V 1 receptor antagonist did not further affect the RSNA inhibition induced by central salt loading. The results suggest that the suppression of RSNA during central salt loading is mainly dependent on the arterial baroreceptors input and the `additive' role of peripheral vasopressin.

Oral physostigmine in alzheimer's disease: Effects on norepinephrine and vasopressin in cerebrospinal fluid and plasma

Physostigmine is a cholinesterase inhibitor which enhances central and peripheral cholinergic activity. In this study, we explored in persons with Alzheimer's disease (AD) the effects of an acute dose of physostigmine in patients receiving chronic physostigmine treatment on the activity of the cholinergically regulated noradrenergic and arginine vasopressin (AVP) systems. Specifically, we estimated the effects of sustained release oral physostigmine on central and peripheral noradrenergic and AVP systems by measuring norepinephrine (NE) and AVP in cerebrospinal fluid (CSF) and plasma. Lumbar punctures were performed in both physostigmine and no drug treatment conditions. In some subjects the effects of physostigmine on the plasma AVP response to the osmolar stimulus of a hypertonic saline infusion also were measured. NE concentrations in both CSF and plasma were significantly lower in the physostigmine than in the no drug condition. AVP concentrations did not differ between conditions in either compartment, nor did physostigmine affect the AVP response to hypertonic saline. Physostigmine appears to decrease both central and peripheral noradrenergic activity in AD.

Anorexia nervosa: directions for future research. Study Group on Anorexia Nervosa.

On September 27-29, 1993, the Study Group on Anorexia Nervosa (AN): Basic Mechanisms, Clinical Approaches and Treatment met in Geneva, Switzerland to discuss recent progress in research on anorexia nervosa, and to identify directions for future studies. Anorexia nervosa is a disorder of unknown etiology, without a specific curative treatment, affecting mostly individuals in adolescence and early adulthood, with significant morbidity and mortality, and having a major impact on psychosocial and vocational development. In anorexia nervosa there are severe disturbances in virtually every endocrine system, such as the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, the hypothalamic-pituitary-thyroid (HPT) axis, the growth hormone (GH)/somatomedin C (IGF-1) system, and the central and peripheral arginine vasopressin (AVP) systems. Furthermore, classical neurotransmitter systems, such as the cholinergic noradrenergic, and serotonergic systems, are abnormally regulated in anorexia nervosa. New research data is also emerging on the abnormal regulation of immune function in this disorder. The Study Group concluded that even though several biological systems are abnormally regulated in anorexia nervosa, there is no biological test which is specific enough to make the diagnosis of the disorder. New directions for research in anorexia nervosa are identified and discussed in this report. Finally, the Study Group proposed future meetings to bring together clinical and pre-clinical (pharmacological, biochemical, and molecular) scientists studying topics, such as neuroendocrine function, which are important in the biology of anorexia nervosa.

Elevated basal adrenocorticotropin and evidence for increased central opioid tone in highly trained male athletes.

Basal cortisol and ACTH levels have previously been shown to be elevated in highly trained athletes, whereas the ACTH response to ovine CRH has been reported to be diminished compared to that in nonathletic controls. Naloxone, a nonselective opioid receptor antagonist, is known to stimulate ACTH and cortisol secretion. The mechanism of this response is thought to be via increased hypothalamic CRH secretion. The aim of this study was to examine basal and naloxone-stimulated levels of hypothalamic-pituitary-adrenal axis hormones in male athletes. Ten highly trained male athletes and 10 nonathletic controls took part in the study. Peripheral venous blood was sampled for cortisol, ACTH, CRH, and arginine vasopressin (AVP) for 2 h before the administration of 20 mg naloxone, i.v., and 15, 30, 45, 60, 90, and 120 min after naloxone treatment. Body mass index was significantly lower in the athletes (P < 0.001). Basal (prenaloxone) ACTH levels were higher in the athletes (P < 0.05), whereas levels of cortisol, CRH, and AVP were similar in both groups. After naloxone treatment, there was a significantly greater rise in ACTH in the athletes (P < 0.02). There was also a trend for the cortisol response to be greater, which was not statistically significant (P < 0.07). Although in both groups, peripheral CRH rose after naloxone treatment (P < 0.005), a rise of similar magnitude occurred over the 2-h period before naloxone (P < 0.0001). Plasma AVP did not change significantly after naloxone treatment. Neither the plasma cortisol level at baseline nor the body mass index correlated significantly with the ACTH or cortisol response to naloxone. The presence of an enhanced ACTH response to naloxone is evidence that central opioid tone may be increased in highly trained athletes. However, there is no associated suppression of the hypothalamic-pituitary-adrenal axis, and basal ACTH levels are raised, without any detectable change in peripheral plasma CRH or AVP. An additional factor (other than CRH) that stimulates ACTH secretion may be released after naloxone administration.

Indomethacin and arginine vasopressin interaction in the fetal kidney: A mechanism of oliguria

Indomethacin has been shown to cause fetal oliguria in humans and animals. This study was designed to test the hypothesis that indomethacin-induced fetal oliguria is mediated through the renal action of arginine vasopressin. Twenty-seven late-gestation (129 +/- 4 days [mean +/- SE]) chronically catheterized fetal sheep were studied. After a 1-hour control period fetal responses to indomethacin, 0.05 mg/kg given intravenously, followed by a 4-hour maintenance infusion (n = 9), were compared with an identical indomethacin infusion plus an arginine vasopressin V2-receptor antagonist (d[CH2]1(5), D-Phe2, Ile4,Arg8,Ala9)-VP (n = 8) or vehicle alone (n = 10). Fetal arterial and venous pressures, heart rate, and urinary flow were measured continuously. Fetal urinary flow rate (p < 0.0001) and free water clearance (p = 0.004) fell in response to indomethacin alone, but the addition of the arginine vasopressin V2-receptor antagonist blocked indomethacin's oliguric and free water effect. Urinary osmolality and sodium increased in both indomethacin and indomethacin+arginine vasopressin V2-receptor antagonist groups compared with vehicle (p < 0.05). Fetal arterial pressure increased in response to indomethacin, and the addition of the arginine vasopressin V2-receptor antagonist potentiated this response (p = 0.007). These results suggest that (1) fetal oliguria secondary to indomethacin is mediated through the stimulation of the renal arginine vasopressin V2-receptor and (2) prostaglandin synthesis inhibition may play a role in renal tubular sodium handling. In addition, the arginine vasopressin V2-receptor plays a role in ameliorating the hypertensive response to indomethacin. We speculate that indomethacin stimulates circulating arginine vasopressin levels and enhances peripheral arginine vasopressin effects in the fetus, resulting in oliguria and hypertension.

Androgen manipulation and vasopressin binding in the rat brain and peripheral organs.

It is now widely recognized that there is a sexual dimorphism in the development of arginine vasopressin (AVP) immunoreactivity in certain parts of the brain, and that changes in brain AVP immunoreactivity change with manipulation of androgen status. The aim of this experiment was to determine specifically any AVP receptor changes in response to manipulation of androgen levels using a selective V1 antagonist radioligand. Following castration, plasma testosterone levels fell and AVP immunoreactivity was reduced in the lateral septum and bed nucleus of the stria terminalis. With testosterone supplementation in castrated animals, the immunoreactivity in these regions was restored to a higher degree than in sham-operated animals. Central and peripheral V1 AVP receptor binding (as determined using the selective AVP V1 antagonist radioligand [125I](d(CH2)5,sarcosine7)AVP was not changed in any of the brain regions studied or in liver or kidney membranes from the three groups. This study demonstrates that there is no change in brain AVP receptor binding despite changes in regional AVP immunoreactivity in the brain, and excludes any confounding interaction with changes in oxytocin receptors.

Does endogenous peripheral arginine vasopressin have a role in the febrile responses of conscious rabbits?

1. The actions of peripheral arginine vasopressin (AVP) on the febrile responses of conscious rabbits induced by peripherally administered polyinosinic:polycytidylic acid (poly(I).poly(C)) have been studied using an AVP V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin). 2. Temperature responses were monitored continuously using rectal thermistor probes. Test substances were administered intravenously (i.v.). Blood samples were taken at timed intervals from a marginal ear vein and plasma PGE2 and PGF2 alpha levels determined by radioimmunoassay. 3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated a reproducible biphasic rise in body temperature with a lag phase of 45-60 min and peaks at 90 and 225 min. The febrile response was accompanied by a 5-fold rise in circulating immunoreactive (ir) PGE2, which peaked after 90 min and remained elevated up to 300 min. Poly(I).poly(C) also stimulated a 2.5-fold rise in circulating irPGF2 alpha, which peaked after 150 min and was followed by a return to basal levels after 300 min. 4. The overall magnitude of the febrile response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. 5. The irPGE2 response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to the pyrogen. The irPGF2 alpha response was only reduced at the peak 150 min time point measurement. 6. In conclusion, these results show a modulatory role for a peripherally administered AVP V1 antagonist in the febrile responses to poly(I).poly(C), suggesting a possible propyretic role for endogenous peripheral AVP. This modulatory role appears to be mediated via actions on prostaglandin E2.

Central and peripheral vasopressin interact differently with sympathetic nervous system and renin-angiotensin system in renal hypertensive rabbits.

This study was designed to elucidate how central and peripheral arginine vasopressin (AVP) interacts with the sympathetic nervous system and the renin-angiotensin system to maintain blood pressure in two-kidney, one-clip hypertensive rabbits. We recorded renal sympathetic nerve activity (RSNA) in the conscious state as an index of sympathetic nervous system function. The changes in mean arterial pressure, heart rate, and RSNA were recorded continuously for 60 minutes after intravenous administrations of captopril (2.5 mg/kg) and nicardipine (3.2 micrograms.kg-1.min-1) in eight identical rabbits. Despite equivalent reductions in mean arterial pressure (10 +/- 1 mm Hg), the increase in RSNA was significantly larger with captopril than that with nicardipine, and the plasma concentration of AVP was elevated (from 100% to 255 +/- 24%) with captopril. Mean arterial pressure was reduced, and RSNA was increased by intravenous infusion of AVP antagonist d(CH2)5Tyr(Me)AVP (n = 8), whereas vertebral artery infusion of the antagonist (n = 6) did not change RSNA. During central and peripheral infusions of AVP antagonist, RSNA was exaggerated by blood pressure reduction with nicardipine as well as with captopril. Increases in RSNA induced by captopril and nicardipine were larger by central infusion of AVP antagonist than by intravenous infusion. The decrease in mean arterial pressure by captopril (30 +/- 4 mm Hg) in eight sinoaortic-denervated hypertensive rabbits was larger than that in hypertensive rabbits with intact baroreflex. These data suggest that compensatory activation of RSNA was revealed by central and peripheral attenuation of AVP and that the sympathetic nervous system became the most important mechanism for blood pressure maintenance in the absence of AVP. The interaction of AVP with the sympathetic nervous system may be independent of the state of the renin-angiotensin system, since the exaggeration of RSNA by AVP antagonist was qualitatively the same with nicardipine as with captopril. In conscious renal-hypertensive rabbits, AVP in the central nervous system played a substantial role when blood pressure was reduced, although it did not contribute to blood pressure maintenance in the basal condition.