Osmoregulation of plasma vasopressin in myxedema

We studied osmoregulation of plasma vasopressin (AVP) in eight patients with untreated myxedema due to primary hypothyroidism. All patients had severe thyroid hormone deficiency due to chronic thyroiditis and had been receiving no medication at the time of this study. AVP release was defined by 5% hypertonic saline infusion test in all patients, and urinary diluting capacity was estimated by the iv water-loading tests in five patients. Plasma AVP was measured by sensitive and specific RIA. The mean basal plasma AVP level in the patients (0.5 +/- 0.1 pmol/L) was significantly lower (P less than 0.01) than that in normal adults (2.5 +/- 0.5 pmol/L). During hypertonic saline infusion, the rise in plasma AVP was normal or subnormal in all patients. In two patients who showed mild to moderate hyponatremia in the basal state and mild urinary diluting defect during water loading, plasma AVP was appropriately suppressed in each case. These results indicate that inappropriate elevation of plasma AVP is not common in myxedema, and that impaired water excretion is due mainly to AVP-independent mechanisms.     

Role of angiotensin II in the aldosterone secretory response to adrenocorticotropin in sodium-restricted normal human subjects.

A study was performed to determine the possible role of angiotensin II (AII) in mediating the increased adrenal aldosterone response to infused alpha 1-24-ACTH, induced by sodium deprivation. Nine normal subjects, aged 18-31 yr. received 8-h infusions of 1) alpha 1-24-ACTH (0.5 U given over 8 h) while on a diet with unrestricted sodium content; 2) saralasin at 0.5 micrograms/kg/min or ACTH alone (0.5 U over 8 h) on the 7th day of a 10 meq sodium diet; and 3) ACTH and saralasin together on the 8th day while still on sodium restriction. AII was administered for the last 2 h of infusion 3. Plasma cortisol and aldosterone concentrations were measured at hourly intervals during the infusions and plasma renin activity was measured at 2 hourly intervals. ACTH infusion produced an increase in the plasma aldosterone concentration which was significantly greater during sodium restriction than when sodium intake was unlimited. This increase was not associated with an ACTH-induced rise in the plasma renin activity and was not significantly altered when ACTH was administered with saralasin. The rise in plasma cortisol concentration induced by ACTH was not significantly different when the normal subjects were on liberal and restricted sodium intakes. It is concluded that AII plays little if any acute role in increasing the stimulatory action of ACTH on aldosterone secretion during sodium restriction.     

Chronic Cardiovascular Effects of Central Vasopressin in Conscious Rats

To clarify the cardiovascular effects of central vasopressin (AVP), a chronic intracerebroventricular (ICV) infusion of AVP was performed in conscious Wistar normotensive rats. Animals were divided into 3 groups: 1) AVP 1 ng/hr (Low), 2) AVP 100 ng/hr (High), and 3) saline (control) ICV infusion. After a 6 day control period, AVP or saline was continuously infused into the lateral cerebroventricle at a rate of 1 μ/hr using osmotic minipump for 7 days. As a result, a dose-related elevation of AVP concentration in CSF was achieved. Systolic blood pressure in both Low and High AVP infusion was slightly (7-12 mmHg) but significantly higher than that in control. ICV infusion of AVP did not alter urine volume, electrolytes excretion or osmolality, and AVP vascular antagonist injected intravenously failed to affect mean arterial pressure. Furthermore, plasma catecholamines and renin activity did not differ significantly among the groups. Thus, chronic ICV infusion of AVP induced the elevation of blood pressure, which is due to centrally mediated effect of AVP.     

Increase in plasma concentrations of atrial natriuretic peptide during infusion of hypertonic saline in conscious newborn calves

Plasma concentrations of atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma concentrations of aldosterone, urine flow rate and sodium and potassium excretion were studied in two groups of four conscious 3-day-old male calves, infused with hypertonic saline or vehicle. Hypertonic saline infusion (20 mmol NaCl/kg body weight) was accompanied by a progressive rise in plasma concentrations of ANP (from 16.5 +/- 0.2 pmol/l at time 0 to 29.3 +/- 3.0 pmol/l at 30 min; P less than 0.05) and by a gradual decrease in PRA (from 1.61 +/- 0.23 nmol angiotensin I/l per h at time 0 to 0.54 +/- 15 nmol angiotensin I/l per h at 90 min; P less than 0.05); there was no change in the plasma concentration of aldosterone. Within the first 2 h of the 24-h urine collection period there was a marked rise in urine flow rate and sodium excretion in treated calves when compared with control animals (66.0 +/- 8.3 vs 15.9 +/- 1.2 ml/kg body weight per 2 h (P less than 0.05) and 6.7 +/- 1.3 vs 0.4 +/- 0.02 mmol/kg body weight per 2 h (P less than 0.01) respectively). During the following 22 h, urinary water and sodium excretion remained at significantly high levels. Thus, in the conscious newborn calf, changes in plasma ANP levels and urinary water and sodium excretion during hypertonic saline infusion are compatible with the hypothesis that endogenous ANP participates, at least in part, in the immediate diuretic and natriuretic renal response induced by the sodium overload.     

INFLUENCE OF NIFEDIPINE AND ENALAPRIL ON OSMOREGULATION OF VASOPRESSIN

To determine whether calcium fluxes and angiotensin II influence osmoregulation of vasopressin (AVP) secretion, the effects of the calcium antagonist nifedipine and of the converting enzyme inhibitor enalapril on the AVP response to an osmotic load were compared to those of a placebo in seven normal female subjects. Plasma and urinary AVP were measured before and during a 3-h infusion of 2.5% hypertonic saline. Nifedipine (10 mg orally 2 h before and 10 mg at the start of the infusion) increased heart rate but did not change blood pressure. The changes in free water clearance and in urinary AVP induced by hypertonic saline under nifedipine were greater than in the control test, but the slope and the intercept of the regression line of plasma AVP upon plasma osmolality were not significantly different. Enalapril (10 mg 3 h before the infusion) did not change heart rate or blood pressure. Free water clearance and urinary AVP did not differ from the control test, but the slope of the regression line was less steep. These slight modifications of the response to an osmotic load suggest that calcium fluxes and angiotensin II only exert a limited influence on AVP osmoregulation in normal females.     

Effects of the nonpeptide V(1) vasopressin receptor antagonist SR49059 in hypertensive patients

We assessed the clinical and pharmacological profile of the orally active V(1) vascular vasopressin (AVP) receptor nonpeptide antagonist SR49059 (SR) during the osmotic stimulation of AVP release in hypertensive patients. In a double-blind crossover-versus-placebo study, 24 untreated stage I or II essential hypertensive patients (12 whites and 12 blacks) received a single 300 mg oral dose of SR 2 hours before the stimulation of AVP secretion with a 5% hypertonic saline infusion. Hemodynamic, humoral, and hormonal parameters were monitored for up to 28 hours after drug administration. SR did not alter blood pressure or heart rate before the saline infusion and did not reduce the blood pressure increment induced by the hypertonic saline infusion. However, the blood pressure peak at the end of the hypertonic saline infusion was slightly lower in the presence of SR (P=0.04). Heart rate was significantly faster between 4 and 6 hours after SR administration (P=0.02). The rise in plasma sodium and osmolality triggered by the saline infusion was not modified by SR, but AVP release was slightly greater in the presence of SR (P<0.0003). AVP-induced aggregation of blood platelets in vitro was significantly reduced by SR, with a peak effect 2 hours after drug administration that coincided with the SR peak plasma concentration. Plasma renin activity and aldosterone before and after the saline infusion were not modified by SR. Urine volume and osmolality were not altered by SR administration. SR effects were similar in the 2 ethnic groups as well as in salt-sensitive versus salt-resistant patients. In a situation of AVP osmotic release and volume expansion in hypertensive patients, a single oral dose of the V(1) vascular AVP receptor nonpeptide antagonist SR49059, which is able to block AVP-induced platelet aggregation, exerts a transient vasodilation effect that is not associated with a sustained blood pressure reduction. SR49059 is a pure V(1) vascular receptor antagonist that is devoid of V(2) renal receptor actions.     

Influence of a prostaglandin inhibitor and a mineralocorticoid on the antidiuretic and hormonal response to an osmolar load

To examine the influence of prostaglandins (PGs) and sodium-volume status on the urinary excretion and action of arginine-vasopressin (AVP), we studied the response to a hypertonic saline infusion (2.5% NaCl, 0.06 ml/kg/min for 3 h) in 8 healthy males under three different conditions: 1) on an ad libitum salt diet (C), 2) after 4-day treatment with indomethacin (IDM) 150 mg/d, 3) after 4-day treatment with fluorohydrocortisone (9 alpha FF) 0.6 mg/d. The rise of urine osmolality and the decrease of free water clearance were identical in all three studies. Basal urinary PGE2, PGF2 alpha and AVP were decreased during IDM and unchanged during 9 alpha FF, compared to C. The increment of urinary AVP was similar during C and IDM but significantly greater with 9 alpha FF (P less than 0.02) although urinary PGs were higher at the end of the infusion. In conclusion, despite markedly different hormonal patterns and sodium status in the three protocols, the antidiuretic response to an osmolar load is preserved suggesting an adaptive mechanism maintaining a constant balance between AVP and PGs.     

Effects of osmotically stimulated endogenous vasopressin on basal and CRH-stimulated ACTH release in man

Two groups of six healthy young males participated in separate experiments to examine the physiological role of endogenous vasopressin in h-CRH-induced (100 micrograms iv) ACTH release: a) after drinking of 3500 ml of water; b) after thirsting for 23 h; c) after 0.9% saline infusion, and d) after 5.0% saline infusion (0.06 ml/kg per min for 120 min). AVP levels were markedly elevated (4 ng/l) after thirsting and 5% saline infusion when compared with water loading or infusion of physiological saline. Although basal and h-CRH-stimulated ACTH and cortisol levels tended to be higher during hypertonic saline infusion and dehydration, no significant difference was observed between states of high or low endogenous AVP levels. These results are not in accordance with previous studies using ovine CRH, which might be due to its longer half-time or the timing of the changes in AVP plasma levels in relation to the CRH injection. Our data suggest that the osmotic modulation performed in this study results in AVP concentrations in the adenohypophysis, which are in the threshold range for influencing ACTH release induced by exogenous h-CRH.     

Renal sensitivity to angiotensin II in the conscious dog

Local formation of angiotensin II (AII) within the kidney has been demonstrated. Changes in renal function induced by inhibitors of the renin-angiotensin system have been the basis for the postulate that AII may act as a paracrine substance in the kidney. We studied the renal action of chronic intrarenal infusions of AII at doses between 2 and 2000 fmol/kg X min in uninephrectomized conscious dogs monitored on 80 meq daily sodium intake. Exogenous AII was confined to the kidney, as demonstrated by the absence of systemic pressor and adrenal cortical responses during the intrarenal infusion. After 2 control days, each dose of AII was infused intrarenally for a period of 3 days. The smallest intrarenal dose of AII that caused significant antinatriuresis and antidiuresis was 20 fmol/kg X min. A significant reduction in urinary volume and sodium excretion occurred during the first 24 h of the infusion period and was proportionate to the amount of peptide infused. Renal escape from the antinatriuretic and antidiuretic effects of the peptide ensued on the second and third days of infusion. There were no significant changes in urinary potassium excretion, plasma renin activity (PRA), plasma aldosterone concentration, or blood pressure throughout the period of intrarenal AII administration. These data demonstrate dose-dependent direct antinatriuretic and antidiuretic actions of low AII concentrations. Escape from the sodium-retaining action of intrarenal AII occurred by 48 h and was independent of suppression of endogenous renin-angiotensin. These results indicate that AII alters renal function by direct intrarenal mechanisms.     

Effects of angiotensin II infusion on the early morning surge of ACTH and o-CRH-provoked ACTH secretion in normal man

The question of whether elevated plasma angiotensin II (AII) levels modulate ACTH secretion in man still awaits a definite answer. We performed two sets of experiments pertinent to that problem: Seven healthy young males each received AII (5 ng/kg/min) and sham infusions on different days in a randomized sequence from 03.00 h to 06.00 h in the morning, while plasma ACTH and cortisol were measured every 20 min. Mean blood pressure rose by about 10 mmHg during AII infusion. Mean plasma ACTH levels were slightly higher with AII than with sham infusion in every single individual (P less than 0.05). Differences in a pre- and post-infusion period were significant. Plasma cortisol levels were almost identical with or without AII infusion. Nine healthy young males received AII (5 ng/kg/min) or sham infusions on different days from 16.30 h to 20.00 h in a randomized sequence and a 100 micrograms o-CRH injection at 17.00 h. Plasma ACTH and cortisol were measured every 15 or 30 min between 16.30 h and 20.00 h. Mean blood pressure rose by about 14 mmHg during AII infusion. The rapid increment and further change in plasma ACTH and cortisol was not significantly different between the AII and sham infusion studies. Conclusions: The dose of AII infused was probably just above the threshold of ACTH stimulation, although AII plasma levels obtained were probably far above the physiological range. On the adrenal level, a vasoconstrictor effect of AII may have prevented stimulation of cortisol. This may be different in states of sodium depletion with reduced vascular effects of AII.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interference in the cytochemical assay of plasma vasopressin by a circulating factor induced by salt-loading in man

Infusion of hypertonic saline into six normal volunteers caused an increase in plasma osmolality from 286.8 +/- 1.7 (mean +/- S.E.M.) to 307.6 +/- 2.6 mosmol/kg (P less than 0.001), a 7.1% increase in estimated blood volume, a rise in plasma immunoreactive arginine vasopressin (AVP) concentrations from 1.3 +/- 0.2 to 12.7 +/- 3.6 pmol/l (P less than 0.001) but no change in plasma AVP concentrations (2.1 +/- 0.9 and 1.9 +/- 1.3 pmol/l) as measured by a cytochemical technique based on the ability of AVP to stimulate rat renal medullary Na+/K+-ATPase activity. Addition of synthetic AVP to plasma obtained before, during and after hypertonic saline infusion also failed to stimulate Na+/K+-ATPase activity. The results suggest that infusion of hypertonic saline interfered with the cytochemical assay for AVP by inhibiting AVP-stimulated medullary Na+/K+-ATPase activity. We conclude that the use of this cytochemical method to detect plasma AVP has severe limitations under these experimental conditions.     

Vasopressin and oxytocin responses to acute and chronic osmotic stimuli in man

The regulation of both arginine vasopressin (AVP) and oxytocin secretion was studied during rapid and prolonged osmotic stimuli in normal adult volunteers. In five subjects given an intravenous infusion of 0.85 mol NaCl at 0.05 ml/kg per min over 2 h there was a significant (P less than 0.05) rise only in plasma AVP, with no significant change in plasma levels of oxytocin. In six further subjects 5 days of restriction to 500 ml fluid daily resulted in significant increases of both plasma and 24-h urinary AVP, whereas there was no change in corresponding oxytocin levels. During another 5-day period in which the same subjects were given an additional 200 mmol sodium as well as having their fluid intake restricted to 1000 ml daily, there were again significant rises in plasma and 24 h urinary AVP with no change in corresponding oxytocin levels. We conclude that, in man, AVP is selectively secreted in response to both dehydration and high sodium intake, whilst even after the stimulus of rapidly increasing plasma osmolality during intravenous infusion of hypertonic saline the rise in oxytocin is not statistically significant. It therefore appears unlikely that oxytocin has a significant role in the physiological control of fluid balance in man.     

Effects of acute water load, hypertonic saline infusion, and furosemide administration on atrial natriuretic peptide and vasopressin release in humans

A new specific RIA for alpha-human atrial natriuretic hormone (alpha hANP) was used to determine whether changes in plasma volume elicited by acute water loading, hypertonic saline infusion, and furosemide administration caused changes in ANP release and resultant changes in renal and cardiovascular function in normal subjects. In addition, changes in plasma arginine vasopressin (AVP), PRA, and aldosterone concentrations were studied simultaneously. Mean plasma alpha hANP and AVP levels were 51.3 +/- 16.0 (+/- SE) and 3.1 +/- 0.6 pg/ml, respectively, in the basal state. Plasma alpha hANP rose to 77.8 +/- 27.6 in response to a 4.5% increase in plasma volume induced by water loading, increased further to 134.1 +/- 28.9 in response to a 23% volume increase induced by hypertonic saline, and fell to 70.2 +/- 15.8 pg/ml in response to a decrease in plasma volume after furosemide treatment (P less than 0.01-0.05). On the other hand, plasma AVP fell to 1.8 +/- 0.1 pg/ml after the water load, rose to 4.1 +/- 0.6 after hypertonic saline, and rose further to 5.8 +/- 0.8 pg/ml after furosemide (P less than 0.01-0.05). Water and hypertonic saline loading decreased PRA, but plasma aldosterone concentrations did not change; subsequent furosemide administration increased both (P less than 0.01-0.05). Arterial pressure and heart rate did not change significantly. Increases in urinary Na excretion and osmolar clearances were associated with a rise in plasma alpha hANP after water loading and hypertonic saline infusion (P less than 0.01-0.05), but changes in urine flow were mainly associated with alterations in AVP release. associated with alterations in AVP release.     

Role of angiotensin II in aldosterone regulation in the Pekin duck

The response of plasma aldosterone to increased plasma angiotensin II (AII) was evaluated in normally hydrated Pekin ducks as well as in birds in which plasma sodium had been acutely increased (+12 mmol/l) or reduced (-4 mmol/l) by the prior infusion of hypertonic saline or hypotonic glucose. In all cases, the i.v. infusion of AII at rates of 5, 15 and 45 pmol/kg per min for 1 h produced dose-dependent increases in the plasma concentration of aldosterone, with a potency that was inversely related to the sodium status. In addition, adrenal receptors for AII were demonstrated by in-vitro autoradiography and membrane-binding techniques, suggesting that the AII effect on aldosterone secretion is direct. Angiotensin II produced no change in plasma corticosterone. The infusion of KCl at 1, 2 and 5 mmol/l for 1 h increased plasma potassium by as much as 2 mmol/l, but had no influence on plasma aldosterone. Similarly, the heptapeptide angiotensin III, infused at 5, 15 and 45 pmol/kg per min for 1 h had no effect on circulating aldosterone. The results show that in ducks, AII has a physiological role in the control of aldosterone, whereas plasma potassium and angiotensin III have no such secretagogue function.     

Increases in plasma ACTH and cortisol after hypertonic saline infusion in patients with central diabetes insipidus.

To clarify the mechanism for the potentiation of CRH-induced ACTH response by the infusion of hypertonic saline, we investigated changes in plasma ACTH concentration after infusion of 5% hypertonic saline in five patients with untreated central diabetes insipidus (DI). Basal levels of plasma ACTH and cortisol in the DI group were not significantly different from those in normal control subjects. The infusion of hypertonic saline produced an increase in plasma arginine vasopressin (AVP) in controls, but did not elevate ACTH. However, in patients with DI, the plasma AVP concentration did not change, but circulating ACTH increased 3.6-fold (7.7 +/- 1.5 to 23.0 +/- 2.7 pmol/liter; P < 0.01), and plasma cortisol also increased significantly (298 +/- 99 to 538 +/- 124 nmol/liter; P < 0.05). Moreover, a positive correlation was observed between plasma ACTH and osmolality (r = 0.72; P < 0.005). These results indicate that ACTH secretion in DI patients is regulated by a mechanism distinct from that in healthy subjects. It seems possible that the increase in plasma osmolality promotes ACTH secretion in DI patients through AVP and/or urocortin via the hypophyseal portal system, independent of the AVP secretion from magnocellular neurons.     

Clearance of vasopressin from cerebrospinal fluid to blood in chronically cannulated Brattleboro rats

The antidiuretic effects of intravenous (i.v.) and intracerebroventricular (i.c.v.) infusions of vasopressin (AVP) were compared in chronically cannulated conscious Brattleboro rats. AVP infused i.c.v. for 6 h reduced urine volume and increased urinary Na+ and K+ concentrations. These antidiuretic responses to i.c.v. AVP were dose related in the range 3-12 ng/h and were delayed and prolonged when compared with i.v. infusions (0.33-3 ng/h) of this peptide. Comparison of the dose-response curves for both routes of administration demonstrated that the antidiuretic response to i.c.v. infusion of AVP was approximately 10-fold lower than to AVP given intravenously. Since measurable amounts of AVP-like material appeared in the urine during the antidiuretic response, we conclude that a significant amount of AVP infused into the cerebroventricular system reaches the bloodstream in a biologically active form.     

LACK OF THIRST, OSMORECEPTOR DYSFUNCTION, EARLY PUBERTY AND ABNORMALLY AGGRESSIVE BEHAVIOUR IN TWO BOYS

Two unrelated boys (C.C. 13 years; J.W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were less than 1 litre and the maximal urinary osmolality was 1232 in C.C. and 950 in J.W. Plasma renin activity was elevated (greater than 2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0.85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour.     

Inhibition of captopril-induced increase in plasma renin activity by propranolol

The inhibition of renin release by angiotensin II (AII) is well documented. However, the interaction of this short loop feedback mechanism of AII with the sympathetic nervous system is still unclear. This study was designed to investigate the possible functional relationship between AII and the beta-adrenergic receptors with respect to renin release in vivo. First, the effect of propranolol on captopril-induced renin release was examined in conscious rats. Secondly, the effect of AII on isoproterenol-induced renin release was determined. Captopril (1 mg/Kg) increased plasma renin activity (PRA) from 1.6 +/- 0.3 ng/ml/hr to 4.5 +/- 0.6 ng/ml/hr (p less than 0.01). In contrast, there was no significant change in PRA in rats which received both captopril and propranolol (before 0.9 +/- 0.2 ng/ml/hr, after 1.3 +/- 0.3 ng/ml/hr). Thus, propranolol attenuated the increase in PRA caused by captopril. Isoproterenol infusion (0.1 micrograms/Kg/min) provoked a significant increase in PRA (before 1.3 +/- 0.4 ng/ml/hr, after 6.6 +/- 1.7 ng/ml/hr, p less than 0.01). AII infusion in combination with isoproterenol also increased PRA from 1.6 +/- 0.4 ng/ml/hr to 5.2 +/- 0.3 ng/ml/hr (p less than 0.01). AII in this dose did not suppress isoproterenol-induced renin release. These results suggest that the beta-adrenergic receptor mediating renin release is functionally located distal to the AII receptor in the short loop mechanism controlling renin release.     

The physiological significance of arginine vasopressin in potentiating the response to corticotrophin-releasing factor in sheep

In order to assess the physiological importance of endogenous arginine vasopressin (AVP) in augmenting the ACTH response to corticotrophin-releasing factor (CRF), the response to CRF during hypertonic saline infusion in six Coopworth sheep was examined. A 4-h infusion of 5% (w/v) NaCl (3.8 ml/min) resulted in significantly (P less than 0.01) greater rises in ACTH and cortisol, but not aldosterone, than were observed after CRF alone. Infusion of hypertonic saline without CRF resulted in a highly significant (P less than 0.001) rise in plasma osmolality and AVP but no significant change in plasma ACTH, cortisol or aldosterone. It is concluded that a marked but physiological increase in peripheral (and presumably central) levels of AVP does not result in any demonstrable change in plasma ACTH concentration. However, under these conditions, the ACTH and cortisol responses to CRF are considerably augmented.     

VASOPRESSIN AND OXYTOCIN RESPONSES TO HYPERTONIC SALINE INFUSION: EFFECT OF THE OPIOID ANTAGONIST NALOXONE

Endogenous opioids inhibit the release of oxytocin (OT) when vasopressin (AVP) is secreted in response to acute pharmacological stimuli in man and to a variety of physiological and pharmacological stimuli to animals. We have investigated the effect of naloxone on the AVP and OT responses to hypertonic saline in man. In two separate studies, six male subjects were infused with hypertonic saline (675 mmol/l, 0.05 ml/kg/min for 2 h) and either naloxone (4 mg bolus and 6 mg/h) or normal saline in random order. Hypertonic saline resulted in similar significant rises of plasma osmolality and AVP in both groups and a small but significant decrease in OT. Thirst sensation was not altered by naloxone. Endogenous opioids do not play an important role in the suppression of OT release when AVP is secreted in response to an osmotic stimulus in man.