The interrelationship between the release of renin and vasopressin as defined by orthostasis and propranolol.

The concentration of both plasma renin and plasma arginine vasopressin rose in normal subjects after an 85 degrees head-up tilt. Plasma renin activity, which increased 70-80% above the supine value, was maximal at 15 or 30 min, whereas the six- to seven-fold increase of plasma arginine vasopressin concentration was observed between 30 and 45 min. Intravenous propranolol administered just before tilt was used to investigate the possibility that the delayed rise of arginine vasopressin was stimulated by renin. Although the response of plasma renin was completely abolished by propranolol, the response of vasopressin was unaffected. These findings suggest that the release of vasopressin that follows isosmolar hypovolemia achieved by orthostasis may occur independently of changes in the renin-angiotensin system in the presence of propranolol.

Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population.

Despite the common use of MDMA (ecstasy) in the UK, the mechanism underlying associated potentially fatal cerebral oedema is unclear. We used a new experimental approach working directly with clubbers to perform a study on 30 (17 male) experienced clubbers (mean 6.6 years of clubbing). Pre- and post-clubbing measurements were performed to compare plasma levels of pituitary hormones (vasopressin, oxytocin), plasma and urine osmolality, urinary pH, and plasma sodium and urea. Ecstasy consumption was confirmed by using urinary drug screening pre- and post-clubbing. MDMA was detected in the urine samples of 17 subjects, three of which tested positive during pre-clubbing tests. Mean plasma vasopressin concentration increased in the MDMA group (1.28 +/- 0.29 to 1.43 +/- 0.41 pmol/l), but fell in other participants (1.23 +/- 0.42 to 1.16 +/- 0.0.34 pmol/l). Similarly, mean plasma oxytocin concentrations increased after ingestion of MDMA (2.02 +/- 0.29 to 2.43 +/- 0.24 pmol/l), but fell in the group that did not use MDMA (2.17 +/- 0.36 pmol/l to 1.89 +/- 0.37 pmol/l). There was a significant group by time interaction for plasma osmolality and plasma sodium (p = 0.001 and p = 0.003, respectively) and between change in urinary osmolality (p < 0.001) and MDMA use, with the pattern of change being consistent with the induction of inappropriate vasopressin secretion (also known as SIADH) by MDMA. This report demonstrates SIADH in ecstasy-using "clubbers", which has important clinical implications.

Melatonin and its analogs inhibit the basal and stimulated release of hypothalamic vasopressin and oxytocin in vitro.

The secretion of neurohypophyseal hormone and ACTH in the rat has been shown to exhibit circadian rhythms, with high values during the day and low values throughout the night. The neurohypophyseal hormone daily rhythm is altered by exposure to constant light and by pinealectomy. It was, thus, proposed that the observed fall in vasopressin (AVP), oxytocin, and ACTH over the hours of darkness could be related to the release of melatonin seen at this time. Therefore, a study was performed to determine the effect of melatonin on AVP, oxytocin, and CRH-41 release from the isolated rat hypothalamus in vitro. Employing a previously validated technique, rat hypothalami were incubated in either medium alone or medium containing melatonin or one of two melatonin analogs. Hormone release was measured by RIA, and the ratios were calculated and compared by Student's t test, with Dunnett's correction for multiple comparisons. Melatonin showed a dose-dependent inhibition of both basal and stimulated AVP and oxytocin release in the concentration range 4.3 x 10(-10) to 2.5 x 10(-3) M, while having no significant effect on the release of CRH-41. The two melatonin analogs, 2-iodomelatonin and 5-methoxy-N-isobutanoyltryptamine, were also found to inhibit both basal AVP and oxytocin release, indicating that this effect probably depends upon the presence of melatonin receptors in the hypothalamus. This inhibitory modulation of AVP, in the absence of any effect on CRH-41, suggests that melatonin may affect water balance by means of directly inhibiting hypothalamic AVP release. Furthermore, circadian rhythmicity in pituitary-adrenal activity may depend on melatonin modulation of AVP, rather than changes in CRH-41.

Differential effects of neuroexcitatory amino acids on corticotropin-releasing hormone-41 and vasopressin release from rat hypothalamic explants.

We have investigated the direct effects of different neuroexcitatory amino acids (EAA) on the secretion of CRH-41 and arginine vasopressin (AVP) from the rat hypothalamus maintained in vitro. CRH-41 and AVP released in the medium were assayed by RIA before and after incubation with N-methyl-D-aspartate (NMDA), N-methyl-D,L-aspartic acid, kainate (KA), and quisqualate in the concentration range 1 nM to 1 mM in either the absence or the presence of 1 mM Mg2+ in the medium. In the case of NMDA, the effect of the addition of glycine (1 and 10 microM) to the incubation medium was also studied. Finally, we investigated whether different periods of exposure (up to 100 min) of hypothalamic explants to NMDA and KA would affect CRH-41 release. While no EAA was able to induce CRH-41 release under any of the above conditions, 20-min incubations with NMDA in the dose range of 1 nM to 1 mM in the absence of added Mg2+ significantly stimulated AVP release in a dose-related fashion; the maximum effect occurred at a concentration of 1 mM [ratio of stimulated collection/basal collection: NMDA, 1.51 +/- 0.10, controls, 0.86 +/- 0.05 (mean +/- SEM); P < 0.001]. KA also showed a dose-related stimulatory effect in the dose range of 1 nM to 1 mM, with maximal AVP stimulation at 10 microM (KA, 1.91 +/- 0.28; controls, 0.90 +/- 0.03; P < 0.01). The effects of both NMDA and KA on AVP were completely reversed by the competitive antagonists D,L-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3 dione, respectively, at doses 10 times higher than those of the agonists. N-Methyl-D,L-aspartic acid stimulated AVP secretion only at a dose of 10 mM (P < 0.01), whereas quisqualate was ineffective at any concentration. The addition of 1 mM Mg2+ to the medium blocked the effect of NMDA, while attenuating AVP stimulation induced by KA. The stimulatory effect of KA on AVP was significantly reduced by D-L-2-amino-5-phosphonovaleric acid (P < 0.05), suggesting that KA may also act through NMDA receptors. Moreover, the presence of glycine in the incubation medium did not result in any effect of NMDA on CRH-41 secretion, nor did it appear to potentiate NMDA-induced AVP release.(ABSTRACT TRUNCATED AT 400 WORDS)

Nitric oxide modulates the release of vasopressin from rat hypothalamic explants.

The enzyme nitric oxide (NO) synthase is present in the paraventricular nucleus, while nitric oxide has recently been shown to inhibit the stimulated release of corticotrophin-releasing hormone (CRH) in vitro. Thus the possible role of NO in regulating, vasopressin (AVP), which also plays an important role in pituitary-adrenal activity, has been investigated. The effects were studied of the NO donors, L-arginine, syndnonimine-1 (SIN-1) and sodium nitroprusside, on both the basal and stimulated release of AVP, employing a previously validated system. Rat hypothalami were incubated in either medium alone or medium containing the test substances and hormone release was measured by RIA. The effect of L-arginine in the presence of the NO synthase inhibitor, L-NMMA, was also investigated. L-arginine reduced KCl-evoked AVP release; this effect was reversed by L-NMMA and reduced by the addition of ferrous human Hb. Similarly, SIN-1 and sodium nitroprusside attenuated KCl-evoked AVP release. L-arginine also reduced IL-1 beta-stimulated AVP release. NO appears to directly and specifically inhibit the stimulated release of AVP from rat hypothalamic explants in vitro, similar to its effects on CRH. These findings provide further evidence that NO may be involved in neuroendocrine regulation.

Localization and actions of cholecystokinin in the rat pituitary neurointermediate lobe.

Rat pituitary neural lobe contained high concentrations of cholecystokinin-like immunoreactivity (CCK-LI). Section of the pituitary stalk resulted in loss of CCK-LI, and both lactation and replacement of drinking water with 2% saline resulted in marked depletion of CCK-LI. Rats with congenital diabetes insipidus (Brattleboro strain) had a 73% reduction in CCK-LI below the levels of hooded Long-Evans controls, where as levels in the brain were unchanged. Release of CCK-LI, labeled dopamine, and gamma-amino butyric acid in response to potassium depolarization was studied. There was a low fractional release of CCK-LI. Addition of sulfated CCK-8 (CCK-8s) to the medium enhanced the calcium-dependent potassium-stimulated release of dopamine, but basal release was unaffected. gamma-Amino butyric acid release was only poorly calcium dependent and not effected by extracellular CCK-8s. Vasopressin and oxytocin release were stimulated by electrical stimulation of the pituitary stalk, and were unaffected by the addition of CCK-8s to the medium. In vivo, however, the injection of 5 micrograms CCK-8s into the third ventricle resulted in increased plasma vasopressin concentrations.

Evidence for endogenous opioid control of vasopressin release in man.

The role of endogenous opioids in the control of vasopressin secretion was studied using the pure opiate antagonist naloxone. Naloxone both reduced resting levels of vasopressin and inhibited the rise in vasopressin induced by an orthostatic stimulus. These results suggest that endogenous opioids are important as a tonic stimulus to vasopressin release in man.

Effects of the opiate antagonist naloxone and the enkephalin analog DAMME on the vasopressin response to a hypertonic stimulus in man.

Experiments were performed to study the effects of opioids on both the plasma arginine vasopressin and renal responses to hypertonic saline. Neither the opiate antagonist naloxone nor the enkephalin agonist DAMME [D-Ala2, MePhe4, Met (0)-ol)enkephalin] altered the vasopressin response to the same hypertonic stimulus, although DAMME increased free water clearance. In man, opioids do not seem to be important mediators of the vasopressin response to osmolar change.

The effects of intravenous administration of cholecystokinin on feeding behaviour and release of pituitary hormones in pigs are not mediated by serotonergic (5-HT3) receptors.

Two experiments were carried out using the serotonergic (5-HT3) antagonist ondansetron (GR 38032F) to investigate whether the actions of peripherally-administered cholecystokinin octapeptide (CCK) in the prepubertal pig might involve 5-HT3 receptors. In Experiment 1, it was shown that ondansetron (10 or 30 mg, i.v.) did not affect the initial feeding response and did not modify the behavioural inhibition induced by a subsequent injection of CCK (1.3 microgram/kg, i.v.). In Experiment 2, it was demonstrated that the nauseogenic action of CCK, indicated by its stimulatory effect on release of vasopressin and cortisol, was not markedly altered by ondansetron (30 mg, i.v.). These results suggest that 5-HT3 receptors play a negligible part in mediating the behavioural and endocrine responses induced by bolus intravenous injections of CCK in this species.

Endotoxin stimulates an endogenous pathway regulating corticotropin-releasing hormone and vasopressin release involving the generation of nitric oxide and carbon monoxide.

Although the administration of endotoxin in vivo activates the neuroendocrine stress axis in the process of crosstalk between the immune and endocrine axes, the direct application of endotoxin to the hypothalamus in vitro does not stimulate the release of the hypothalamic peptides controlling the hypothalamo-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and vasopressin. The hypothesis has therefore been tested that endotoxin may also activate inhibitory pathways, specifically those involving the generation of nitric oxide (NO) and carbon monoxide (CO). Studies were performed on the isolated rat hypothalamus using endotoxin in the presence or absence of inhibitors of heme oxygenase (which generates CO) and nitric oxide synthase, and ferrous hemoglobin. Endotoxin alone decreased both CRH and vasopressin secretion from the hypothalamus. However, when applied together with a nitric oxide synthase inhibitor, the inhibitory effect on CRH was lost. Conversely, co-administration with heme oxygenase inhibitors transformed the inhibition of vasopressin to stimulation, while having no effect on the inhibition of CRH. Ferrous hemoglobin reversed the inhibition of vasopressin, but did not lead to stimulation. It is therefore concluded that endotoxin may stimulate endogenous pathways that lead to the generation of NO, which in turn inhibits CRH. In addition, it generates CO, which modulates the release of vasopressin. These gases are thus potential counter-regulatory controls to the activation of the HPA.

Regional expression of c-fos antigen in the basal forebrain following intraventricular infusions of angiotensin and its modulation by drinking either water or saline.

The expression of c-fos protein was examined in the basal forebrains of male rats 60 min following intracerebroventricular infusions of 250 pmol angiotensin II. Levels of corticosterone and vasopressin were also measured at the same time point. In animals not allowed access to water after infusion, angiotensin II induced intense c-fos expression in a band of neurons extending throughout the anterior region of the third ventricle region, including the organum vasculosum of the lamina terminalis, the median preoptic nucleus (nucleus medianus) and the subfornical organ. There were also high levels of expression in the hypothalamic supraoptic nucleus and the paraventricular nucleus, particularly its lateral (magnocellular) region, though other, parvicellular areas were also affected. No other area of the hypothalamus was altered. There was increased c-fos expression in the central nucleus of the amygdala and the bed nucleus of the stria terminalis. Allowing rats to drink during the 60-min survival period modified this pattern of response. c-fos was markedly reduced in the supraoptic nucleus and the paraventricular nucleus but not in the other areas examined, including the anterior region of the third ventricle and the amygdala. When water was withheld for 15 min, but then allowed, rats drank the same total volume but c-fos expression was no longer inhibited in either the supraoptic nucleus or paraventricular nucleus. When rats were given 0.9% saline to drink, they ingested about three times as much as water, but angiotensin II-induced c-fos expression was similar to that in rats denied access to water. The pattern was similar following access to 1.8% saline, though levels in the organum vasculosum of the lamina terminalis were reduced. There was a marked correlation between the number of c-fos-positive neurons in the supraoptic nucleus or paraventricular nucleus and plasma levels of corticosterone 60 min after infusion, but not with arginine-vasopressin levels. These experiments show that angiotensin II induces highly localized expression of c-fos in areas known to be concerned with the dipsogenic and endocrine actions of this peptide, and that this pattern is selectively altered by allowing the animal to drink solutions of different tonicity. Immediate-early gene expression is a novel and valuable method of determining the neural response to peptides at the cellular level.

Variations in oxytocin secretion during the 4-day oestrous cycle of the rat.

Oxytocin concentrations in the plasma, pituitary and hypothalamus of female rats were determined in the morning and evening over the 4-day oestrous cycle. Vasopressin concentrations were also determined to allow calculation of the ratios of the two hormones. The results were compared with those from male rats. Plasma oxytocin concentrations were significantly higher in the evening than in the morning on the day of oestrus. Although the evening concentration achieved was similar on each day of the cycle, morning plasma oxytocin concentrations showed a progressive rise from oestrus to pro-oestrus so that no significant diurnal increases were observed on the other days of the cycle. Vasopressin concentrations in the plasma were also seen to increase over the days of oestrus, dioestrus day 1 and dioestrus day 2. On pro-oestrus the plasma concentrations of vasopressin remained unchanged. The ratio of oxytocin:vasopressin fell during the light hours of the cycle. The hypothalamic content of both hormones showed a rise during the hours of daylight parallel to that seen in the plasma, whereas the pituitary content fell over the same period. The diurnal pattern of hormone release observed in male rats was similar to that in females at oestrus. However, the plasma oxytocin concentrations were significantly higher in the male. The plasma clearance rate of vasopressin did not vary significantly during the oestrous cycle. However, the plasma clearance rate for oxytocin did show significant variation, being highest on dioestrus day 1 and lowest on dioestrus day 2.

Kappa-opioid modulation of vasopressin secretion in conscious rats.

A series of studies has been performed in the conscious rat to investigate the effect of the intracerebroventricular (i.c.v.) administration of the selective kappa-opioid receptor agonist, U50 488H, on arginine vasopressin (AVP) secretion stimulated by i.c.v. administration of hypertonic NaCl. Similarly, the effect of the i.c.v. administration of morphine and the i.v. administration of naloxone on AVP secretion was investigated. The response of AVP to an i.c.v. injection of hypertonic NaCl was potentiated by naloxone at a dose of 0.4 mg/kg, but a higher dose (1.2 mg/kg) was required to increase the basal plasma concentration of AVP. Prior treatment with U50 488H or morphine attenuated the increase in plasma concentrations of AVP stimulated by i.c.v. injection of hypertonic NaCl from 13.92 +/- 4.44 to 1.22 +/- 0.34 and 1.78 +/- 0.74 pmol/l respectively (n = 7; P less than 0.05). Prior administration of U50 488H also attenuated the potentiating effect of naloxone on AVP secretion stimulated by i.c.v. injection of hypertonic NaCl. These results indicate that basal AVP secretion is under tonic inhibitory control by dynorphin, and that mu- and kappa-opioid receptors mediate an inhibitory influence of endogenous opioids on osmoreceptor-mediated AVP secretion.

Renal responses to oxytocin during the 4 days of the oestrous cycle in the rat.

Oxytocin was administered to virgin female rats at doses of 25-200 pmol/min during 0.077 mol NaCl/l infusion at 150 microliters/min on each day of the oestrous cycle. The resultant rates of urine flow, glomerular filtration (GFR) and electrolyte excretion were determined. Oxytocin caused significant increases in urine flow (P < 0.001) and sodium excretion (P < 0.001); both responses being dose-dependent (P < 0.02 and P < 0.01 respectively). Significant variations in the renal responsiveness to the hormone occurred over the 4 days of the oestrous cycle. On oestrus the lowest dose of 25 pmol oxytocin/min produced a significant increase in urine flow (from 139.5 +/- 4.3 to 165.6 +/- 7.1 microliters/min, P < 0.005) and a dose of 50 pmol/min produced a significant increase in sodium excretion (from 10.6 +/- 0.1 to 14.5 +/- 0.7 mumol/min, P < 0.005). Significant increases in urine flow and sodium excretion were seen on pro-oestrus with hormone administration rates of 50 and 100 pmol/min respectively and on dioestrus day 2 with a rate of 100 pmol/min. On dioestrus day 1 no increase in urine flow or sodium excretion was seen over the dose range of oxytocin administration. A dose of 100 pmol oxytocin/min significantly increased GFR on pro-oestrus and dioestrus day 2, but not on the other 2 days of the cycle. The circulating hormone concentrations produced by oxytocin infusion were similar on each day of the cycle and so could not account for the differences seen. Therefore, these results suggest varying renal responsiveness to oxytocin during the reproductive cycle of the female rat.

Effect of ovariectomy and treatment with ovarian steroids on vasopressin release and fluid balance in the rat.

Plasma vasopressin concentrations have previously been shown to vary during the oestrous cycle of the rat, being highest on the morning of pro-oestrus and lowest on dioestrus day 1. To determine the effect of gonadal steroids on vasopressin secretion and fluid balance, mature rats were ovariectomized and given oestrogen, progesterone or vehicle alone s.c. for periods of up to 16 days. Plasma vasopressin concentrations fell after ovariectomy and this was reflected in an increase in 24-h urine volume. The normal increase in plasma vasopressin concentrations seen over day-light hours was also suppressed. The change in vasopressin concentrations observed on steroid treatment depended upon both the dose and the duration. High doses of oestrogen were associated with a fall in plasma vasopressin, probably as a result of fluid retention. Thus, of an initial group of rats given silicone elastomer implants containing 50, 500 or 1000 micrograms oestradiol in oil, plasma vasopressin concentrations were reduced after 7 days treatment with 1000 micrograms oestradiol implants in association with reduced plasma sodium concentrations. Daily s.c. injections of 100 micrograms oestradiol benzoate/100 g body weight produced an immediate small increase in plasma vasopressin concentrations, but by 14 days the plasma concentrations of 0.7 +/- 0.16 pmol/l (mean +/- S.E.M.) had fallen significantly and were less than those in the vehicle-treated group (1.2 +/- 0.26 pmol/l). However, after treatment for 14 days with implants containing only 50 micrograms oestradiol, plasma vasopressin concentrations were higher compared with the group receiving vehicle alone, despite the fact that the plasma osmolality was lower in the latter group, suggesting a long term resetting of the osmoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Pituitary and plasma vasopressin concentrations and fluid balance throughout the oestrous cycle of the rat.

Observations were made of fluid balance and vasopressin concentrations throughout the oestrous cycle of normally cyclic female rats housed under a 12 h light: 12 h darkness regime. Plasma vasopressin concentrations were found to increase progressively during the light period, falling again during the night on all days of the cycle except pro-oestrus. On this day, peak vasopressin concentrations of 3.32 +/- 0.8 pmol/l were seen between 10.00 and 12.00 h, with lower concentrations of 1.74 +/- 0.22 pmol/l being seen between 18.00 and 19.00 h. Urine flow appeared to reflect the changes in plasma vasopressin concentrations, being significantly lower during the light phase, with a small increase being seen over this period on pro-oestrus. Pituitary vasopressin concentrations were highest between 09.00 and 10.00 h and fell progressively over each of the 4 days of the oestrous cycle. The changes in pituitary content were greater than could be accounted for in terms of the alterations in the plasma concentrations of vasopressin.

Release of vasopressin in response to hypoxia and the effect of aminergic and opioid antagonists.

Plasma vasopressin, arterial blood gas tensions, pH, arterial blood pressure, heart rate and respiration were monitored in conscious rats breathing room air or exposed to varying degrees of hypoxia. A similar series of observations was made in a group of anaesthetized rats and in rats treated with alpha- and beta-adrenergic and dopaminergic blocking agents. The effect of two opioid antagonists on the vasopressin response was also noted. Hypoxia produced an increase in circulating vasopressin concentrations in both conscious and anaesthetized rats. In the conscious animals the increase reached statistical significance when the animals were exposed to 12% oxygen in nitrogen, which produced a fall in arterial PaO2 of 44.7 +/- 5.0%. Guanethidine, phentolamine and propranolol all produced a significant fall in the basal concentrations of vasopressin, while guanethidine, phenoxybenzamine and propranolol blocked the increase seen on breathing 12% oxygen in nitrogen. Naloxone and levallorphan also reduced the vasopressin response to hypoxia. Thus it appears that aminergic pathways play a role in the maintenance of circulating concentrations of vasopressin and in the response to hypoxia. Endogenous opioids also appear to be involved in the hypoxic response.

The influence of reproductive status on vasopressin release in the rat.

It has been shown that surgical ovariectomy of the rat results in a fall in plasma vasopressin concentrations suggesting that ovarian steroids may influence hormone release. To determine whether a similar fall is found on suppression of the oestrous cycle, vasopressin concentrations were monitored after treatment with the antioestrogen preparation tamoxifen or a long-acting analogue of LH-releasing hormone (LHRH) which suppresses ovarian function. Treatment with either agent was found to result in a fall in circulating vasopressin concentrations, with little effect on fluid balance. To determine whether the ovary could influence the vasopressin release in response to known stimuli, hormone concentrations were measured in ovariectomized animals during extracellular fluid hypertonicity produced by an i.p. injection of hypertonic saline and hypovolaemia produced by an i.p. injection of polyethylene glycol. It was found that after ovariectomy or treatment with tamoxifen, the response to hypertonicity was unaffected but that to hypovolaemia was attenuated. Treatment with LHRH affected the response to both hypovolaemia and hypertonicity.

The natriuretic actions of vasopressin in the female rat: variations during the 4 days of the oestrous cycle.

The renal actions of vasopressin were studied in the conscious female rat. Vasopressin caused a dose-dependent increase in sodium excretion when administered at 40-160 pmol/min. The highest dose, which increased sodium excretion from 10.4 +/- 0.3 mumol/min (n = 32) to 18.3 +/- 0.8 mumol/min (n = 8, P < 0.001), also caused a significant rise in glomerular filtration rate (GFR). The antidiuretic and natriuretic responses to vasopressin varied significantly over the 4 days of the oestrous cycle. Both responses were greatest on pro-oestrus, being -57 +/- 3 and 52 +/- 3% above the control values with 80 pmol vasopressin/min. Responses of similar magnitude were also seen on dioestrus day 1. On these two cycle days the effects on urine flow and sodium excretion were accompanied by a significant increase in GFR. Smaller antidiuretic and natriuretic responses were seen on oestrus and dioestrus day 2, without concomitant changes in GFR. As the plasma vasopressin concentrations produced by hormone infusion were similar on each day of the cycle, the renal responsiveness to vasopressin appears to vary over the 4 days of the oestrous cycle. This may be important in terms of alteration and possible disturbances of fluid balance which may occur during reproductive cycles and pregnancy.

Variations in plasma concentrations of vasopressin during the menstrual cycle.

Plasma vasopressin concentrations, determined by radioimmunoassay, were followed throughout the menstrual cycle in eight healthy women. The concentrations were found to depend on the day of the menstrual cycle. The mean concentration on day 1 was 0.5 +/- 0.08 (S.E.M.) microunits/ml, while that on days 16-18 was 1.1 +/- 0.16 microunits/ml. These values were significantly (P less than 0.02) different. Vasopressin release in women may thus depend on the hormonal changes during the menstrual cycle.