Increase In Plasma Vasopressin Concentration Research Articles

Mechanisms Involved in Dual Vasopressin/Apelin Neuron Dysfunction during Aging

Normal aging is associated with vasopressin neuron adaptation, but little is known about its effects on the release of apelin, an aquaretic peptide colocalized with vasopressin. We found that plasma vasopressin concentrations were higher and plasma apelin concentrations lower in aged rats than in younger adults. The response of AVP/apelin neurons to osmotic challenge was impaired in aged rats. The overactivity of vasopressin neurons was sustained partly by the increased expression of Transient receptor potential vanilloid2 (Trpv2), because central Trpv blocker injection reversed the age-induced increase in plasma vasopressin concentration without modifying plasma apelin concentration. The morphofunctional plasticity of the supraoptic nucleus neuron-astrocyte network normally observed during chronic dehydration in adults appeared to be impaired in aged rats as well. IL-6 overproduction by astrocytes and low-grade microglial neuroinflammation may contribute to the modification of neuronal functioning during aging. Indeed, central treatment with antibodies against IL-6 decreased plasma vasopressin levels and increased plasma apelin concentration toward the values observed in younger adults. Conversely, minocycline treatment (inhibiting microglial metabolism) did not affect plasma vasopressin concentration, but increased plasma apelin concentration toward control values for younger adults. This study is the first to demonstrate dual vasopressin/apelin adaptation mediated by inflammatory molecules and neuronal Trpv2, during aging.

The osmotically and histamine-induced enhancement of the plasma vasopressin level is diminished by intracerebroventricularly administered orexin in rats

The effects of the centrally administered neuropeptides orexin-A on water intake and vasopressin (VP) secretion were studied in male Wistar rats (180-250g). Different doses (10, 30, and 90μg/10μl) of the orexins and the specific orexin receptor-1 (OX(1)) antagonist SB 408124 (30μg/10μl) were administered intracerebroventricularly (i.c.v.) under anaesthesia, and the water consumption was measured during 6h. A plasma VP level elevation was induced by histamine (10mg/kg) or 2.5% NaCl (10ml/kg) administered intraperitoneally (i.p.). The plasma VP levels were measured by radioimmunoassay. Increased water consumption was observed after the administration of 30μg/10μl orexin-A. There were no changes in basal VP secretion after the administration of different doses of the orexins. A significant increase in plasma VP concentration was detected following histamine administration. After 2.5% NaCl administration, there was a moderate VP level enhancement. Intracerebroventricularly administered orexin-A (30μg/10μl) blocked the VP level increase induced by either histamine or 2.5% NaCl administration. The inhibitory effects were prevented by the specific OX(1) receptor antagonist. In conclusion, the orexins increased water consumption. After 30μg/10μl orexin-A administration, the polydipsia was more pronounced. The OX(1) receptor antagonist significantly decreased the polydipsia. Histamine or hyperosmotic VP release enhancement was blocked by previously administered orexin. This inhibition was not observed following OX(1) receptor antagonist administration. Our results suggest that the effects of the orexins on water consumption or blockade of the histamine and osmosis-induced VP level increase are mediated by the OX(1) receptor.

Hemodynamic effects in dogs anesthetized with isoflurane and remifentanil-isoflurane

To compare hemodynamic effects in dogs anesthetized with remifentanilisoflurane and with isoflurane alone. 6 adult dogs. Mechanically ventilated, isoflurane-anesthetized dogs received increasing constant rate infusions (CRIs) of remifentanil (0.15, 0.30, 0.60, and 0.90 μg/kg/min) or physiologic saline (0.9% NaCl) solution (control treatment), with a 1-week washout interval between treatments. Each CRI of remifentanil or saline solution was maintained for 60 minutes with equipotent end-tidal isoflurane concentrations that corresponded to 1.3 times the minimum alveolar concentration. Hemodynamic measurements and plasma vasopressin concentrations were determined before and at the end of each CRI and 60 minutes after the end of the infusion regimen. Compared with the control treatment, remifentanil CRIs significantly decreased heart rate (HR) and cardiac index (CI) and significantly increased systemic vascular resistance index (SVRI) and plasma vasopressin concentration. Greatest differences in mean values between treatments were recorded for remifentanil at 0.60 μg/kg/min (HR and Cl were 55% and 47% lower, respectively, and SVRI was 91% higher than for the control treatment). Mean arterial pressure increased significantly during the highest remifentanil CRI (9% higher than for the control treatment). The increase in vascular resistance was positively correlated with increases in vasopressin concentrations (coefficient of determination, 0.65) during anesthesia with remifentanil-isoflurane. Anesthesia maintained with remifentanil-isoflurane may decrease tissue perfusion as a result of a decrease in Cl. However, hypotension may not develop because of systemic vasoconstriction. An increase in plasma vasopressin concentration was associated with the vasoconstriction observed in dogs anesthetized with remifentanil-isoflurane.

Stimulus for vasopressin release during elective intra-abdominal operations.

In 12 patients undergoing an upper abdominal operation, blood pressure and peripheral venous blood samples were taken at intervals throughout the procedure. There was no significant increase in plasma vasopressin concentration after induction of anaesthesia or skin incision; within 3 min of opening the peritoneum and commencing intraperitoneal manipulation there was a highly significant rise (P less than 0.01), maintained with fluctuations until closure of the abdomen. There was no correlation between the changes of blood pressure and those in plasma vasopressin level. In 16 patients undergoing elective cholecystectomy similar observations were made to coincide with events believed, on the basis of the first study, to be related to changes in the concentration of vasopressin. There was a significant rise in vasopressin concentration (P less than 0.01) after incision of the peritoneum, 1 min after the start of intraperitoneal manipulation (P less than 0.01) and after deliberate traction on the stomach (P less than 0.01). During operative cholangiography, when there was no intraperitoneal manipulation, there was a significant fall in the vasopressin level. There was no correlation between changes in vasopressin concentration and blood pressure. These findings indicate that during an abdominal operation nervous stimuli, arising from within the peritoneal cavity and probably mediated via the autonomic system, are an important factor responsible for the increased secretion of vasopressin, and, at least in the absence of major changes in blood pressure and osmolality, the determinant factor.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Effect of the vasopressin receptor antagonist conivaptan in rats with heart failure following myocardial infarction

Myocardial infarction often induces congestive heart failure accompanied by a significant increase in plasma vasopressin concentration. To delineate the role of vasopressin in the pathogenesis of congestive heart failure, the acute hemodynamic and aquaretic effects of conivaptan (YM087, 4′-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5- d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride), a combined vasopressin V 1A and V 2 receptor antagonist, were assessed in rats with heart failure induced by myocardial infarction. Left coronary artery ligation resulted in decreased left ventricular systolic pressure and first derivatives of left ventricular developed pressure, as well as increased left ventricular end-diastolic pressure, lung and right ventricular weight. Single oral administration of conivaptan (0.3 to 3.0 mg/kg) dose-dependently increased urine volume and decreased urine osmolality in heart failure rats. Furthermore, conivaptan (3.0 mg/kg) attenuated the changes in left ventricular end-diastolic pressure, lung and right ventricular weight induced by heart failure while reducing blood pressure. These results show that vasopressin plays a significant role in elevating vascular tone through vasopressin V 1A receptors and plays a major role in retaining free water through vasopressin V 2 receptors in this model of congestive heart failure. Additionally, conivaptan, with its dual vasopressin V 1A and V 2 receptor-inhibiting properties, could exert a beneficial effect on cardiac function in the congestive heart failure rat model.

Inducible nitric oxide synthase pathway in the central nervous system and vasopressin release during experimental septic shock.

Septic shock is characterized by arteriolar vasodilation and hypotension. We have tested the hypothesis that nitric oxide arising from inducible nitric oxide synthase in the central nervous system is responsible for the deficiency in vasopressin release and consequent hypotension during experimental septic shock. Septic shock was induced in male Wistar rats by intravenous injection of 1.5 mg/kg lipopolysaccharide. After lipopolysaccharide administration, we found a significant decrease in mean arterial pressure with a concomitant increase in heart rate, a significant decrease in diuresis, and a transitory decrease in body temperature. An increase in plasma vasopressin concentrations occurred in these animals and was present for 2 hrs after lipopolysaccharide administration, returning close to basal concentrations thereafter and remaining unchanged for the next 24 hrs. When lipopolysaccharide was combined with central administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, we observed a sustained increase in plasma vasopressin concentration and in the maintenance of blood pressure at 4 and 6 hrs after lipopolysaccharide treatment compared with rats treated with lipopolysaccharide alone. These data indicate that central nitric oxide arising from the inducible nitric oxide synthase pathway plays an important inhibitory role in vasopressin release during experimental septic shock and may be responsible for the hypotension occurring in this vasodilatory shock.

Central orexin-A augments sympathoadrenal outflow in conscious rabbits.

We determined the cardiovascular and neurohormonal responses to intracerebroventricular administration of orexin-A in conscious rabbits. Intracerebroventricular injection of orexin-A elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity. Peak values of mean arterial pressure and renal sympathetic nerve activity induced by intracerebroventricular injection of 100 pmol of orexin-A (14.0+/-0.7 mm Hg and 55.4+/-14.9%, respectively) were obtained at 40 and 25 minutes after injection, respectively. Plasma epinephrine and glucose concentrations were significantly increased at 60 and 90 minutes after intracerebroventricular injection of orexin-A (control versus 90 minutes; for epinephrine, 38.0+/-12.8 versus 167.5+/-42.5 pg/mL, P<0.01; for glucose, 6.66+/-0.18 versus 7.75+/-0.14 mmol/L, P<0.01). Plasma norepinephrine and insulin concentrations increased at 60 and 90 minutes but did not attain significant values. Intracerebroventricular injection of orexin-A also caused significant increases in plasma vasopressin concentrations. However, pretreatment with an intravenous injection of pentolinium (5 mg/kg), a ganglion-blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of orexin-A (100 pmol) used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular orexin-A acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.

Effect of dehydration on gastrointestinal function at rest and during exercise in humans.

Dehydration leads to the aggravation of gastrointestinal (GI) complaints during exercise. The aim of this study was to examine the effect of dehydration on various GI parameters during strenuous exercise. Ten healthy well-trained men were investigated in dehydrated and in euhydrated conditions. Dehydration took place before the experiments using a dehydration regimen in a sauna leading to a 3% loss of body mass. Each experiment consisted of 1 h pre-exercise rest, 1.5 h cycling at 70% maximal exercise intensity, and 3.5 h post-exercise rest. During cycling, liquid gastric emptying (GE), orocaecal transit time (OCTT) and intestinal permeability and glucose absorption were measured. The GI-symptoms were scored using a questionnaire. Body temperature, plasma volume and vasopressin were measured before and after cycling. The GE was significantly slower during dehydration [median time to peak 13C enrichment in the breath sample (13C-TTP) 23.6 min, range 13.7-50.0 min, P = 0.02] than in the control situation (median 13C-TTP 17.1 min, range 9.8-38.4 min). The OCTT was unchanged (median 173 min, range 98-263 min compared to median 128 min, range 98-195 min, P = 0.18). Dehydration did not change intestinal permeability, glucose absorption, plasma volume, rectal temperature or plasma vasopressin concentration. In the dehydration experiment, exercise induced a significant increase in nausea (P = 0.01) and epigastric cramps (P = 0.05), in contrast to the control situation. In both experiments, exercise led to a significant increase in rectal temperature and plasma vasopressin concentration, and a significant decrease in plasma volume. The increase in plasma vasopressin concentration was significantly higher in the dehydration experiment (P = 0.015). No significant differences in either the post-exercise rectal temperatures or in plasma volumes was observed. The difference in GE between the two experiments was significantly correlated with the difference in nausea score (r = 0.87, P = 0.002). We concluded that dehydration leads to a delayed GE but not to differences in OCTT, intestinal permeability or glucose uptake during intense cycling. The delay in GE is significantly associated with an increase in exercise-induced nausea.

Central Orexin-A Augments Sympathoadrenal Outflow in Conscious Rabbits

63 Factors regulating food intake, such as leptin and neuropeptide Y, have been shown to participate in central cardiovascular and sympathetic regulations. Orexin-A is a newly discovered hypothalamic peptide that stimulates food intake. The aim of the present study was to determine the neurohormonal and cardiovascular responses to intracerebroventricular administration of orexin-A in conscious rabbits with chronically instrumented electrodes on the renal sympathetic nerve. The experiments were carried out at least 3 days after the surgical procedures. Intracerebroventricular injection of orexin-A elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity (RSNA). Peak values of mean arterial pressure and RSNA induced by intracerebroventricular injection of 100 pmol of orexin-A (+14.0±0.7 mmHg and +55.4±14.9 %) were obtained at 40 and 25 minutes after injection, respectively. Plasma epinephrine and glucose concentrations significantly increased at 60 and 90 min after intracerebroventricular injection of orexin-A (control vs. 90 min; epinephrine: 38.0±12.8 vs. 167.5±42.5 pg/ml, p&lt;0.01; glucose: 6.66±0.18 vs. 7.75±0.14 mmol/l, p&lt;0.01). Plasma norepinephrine and insulin concentrations increased at 60 and 90 min, but did not reach the significant values. Intracerebroventricular injection of orexin-A also caused significant increases in plasma vasopressin concentrations. However, pretreatment with intravenous injection of pentolinium (5 mg/kg), a ganglion blocking agent, abolished these cardiovascular and neurohormonal responses. On the other hand, intravenous injection of the same dose of orexin-A (100 pmol) as that used in the intracerebroventricular experiment failed to cause any cardiovascular and renal sympathetic nerve responses. These results suggest that intracerebroventricular orexin-A acts in the central nervous system and activates sympathoadrenal outflow, resulting in increases in arterial pressure and plasma glucose levels in conscious rabbits.

Nitric oxide, but not vasopressin V2 receptor-mediated vasodilation, modulates vasopressin-induced renal vasoconstriction in rats.

The renal vascular response to vasopressin and its modulation were evaluated in vivo by infusing the peptide directly into the renal artery of anaesthetized rats. The intra-renal artery (i.r.a) infusion of vasopressin induced a dose-dependent decrease in renal blood flow. Vasoconstriction was obvious at a dose of 3 ng/kg per min and reached a maximum at 100 ng/kg per min. The dose required for a half-maximal response (ED50) was 24+/-4 ng/kg per min (mean+/-SEM, n=8), corresponding to an estimated concentration in renal arterial blood required for a half-maximal response (EC50) of 1.9+/-0.6 nM. Thiobutabarbitone anaesthesia markedly increased plasma vasopressin concentration. This increase was prevented partially by hypotonic hydration of the rats without any change in the renal vascular response to exogenous vasopressin. Vasopressin-induced vasoconstriction dose/response curves were similar in homozygous and heterozygous Brattleboro rats. Infusion of desmopressin (1-1000 ng/kg per min, i.r.a.), a vasopressin V2 receptor-selective agonist, failed to induce renal vasodilation or vasoconstriction. In the presence of SR 49059 (1 mg/kg i.v.), a vasopressin V1A receptor antagonist that completely abolished the vasopressin-induced renal vasoconstriction, desmopressin again failed to induce vasodilation. Inhibition of nitric oxide synthase by N(omega)-nitro-L-arginine (L-NNA, 100 microg/kg for 10 min and 7.5 microg/kg per min, i.r.a.) enhanced vasopressin-induced renal vasoconstriction (EC50 0.6+/-0.1 nM, P<0.05). In contrast, cyclooxygenase blockade by indomethacin (5 mg/kg, i.v.) neither modified the vasopressin-induced decrease in renal blood flow nor altered the potentiation of vasoconstriction by L-NNA. These results show that the constrictor response of the rat renal vascular bed in vivo is observed only with high local concentrations of vasopressin. This hyporeactivity in vivo was not explained by an anaesthesia-elicited increase in endogenous vasopressin, nor by a modulatory effect linked to V2 receptor activation or prostanoid release. In contrast, NO release contributed to the attenuation of vasopressin-induced renal vasoconstriction.

Osmoregulation in clinical disorders of thirst appreciation

Thirst and drinking are essential components of normal osmoregulation in healthy man. Abnormalities of thirst appreciation, in particular hypodipsia, have profound implications for water homeostasis. The combination of cranial diabetes insipidus and hypodipsia can have particularly serious consequences, with the potential for life-threatening hyponatraemia. Although the tools for measuring thirst are subjective and lack true specificity, their use in clinical research has contributed greatly to our understanding of the physiology of thirst appreciation and the abnormal control of thirst in osmoregulatory disorders. The precise neural control of thirst appreciation remains unknown, and perhaps as a result of this, satisfactory therapies for the treatment of disorders of thirst have not yet been developed; behavioural modification and retraining of drinking habits remain the rather limited cornerstones of management.

Vasopressin and oxytocin release during prolonged environmental hypoxia in the rat.

BACKGROUND: The mechanism causing peripheral oedema in hypoxaemic chronic obstructive pulmonary disease has not been established. Vasopressin, a powerful antidiuretic hormone involved in salt and water homeostasis, is released in...

Release of vasopressin in response to altered plasma volume and sodium concentrations following pinealectomy in the rat.

Pinealectomy has been shown to alter daily rhythms of neurohypophysial hormone release, with plasma hormone concentrations being elevated in the morning, as compared to intact rats. To determine whether pineal removal also altered the response to known stimuli of hormone release, vasopressin concentrations were measured in control, sham-operated, and pinealectomized animals during extracellular fluid hypertonicity produced by an intraperitoneal (i.p.) injection of hypertonic saline or hypovolaemia produced by an i.p. injections of polyethylene glycol. In the combined sham-operated and unoperated groups, injection of hypertonic saline produced a marked increase in plasma vasopressin concentrations from 2.18 +/- 0.28 to 7.2 +/- 1.24 pmol/liter, but the response was attenuated in pinealectomized animals, concentrations increasing to only 3.4 +/- 1.2 pmol/liter. Similarly, following infusion of hypertonic saline, the increase in plasma vasopressin per unit increase in plasma sodium was lower in pinealectomized animals than the pineal intact controls. The response to hypovolaemia was also attenuated, plasma hormone concentrations following reduction in blood volume of approximately 10% increasing to only 3.6 +/- 0.6 pmol/liter as compared to 7.3 +/- 2.2 pmol/liter in the control groups. There were no significant differences in pituitary vasopressin content in any of the groups studied. Thus, the pineal may influence the vasopressin response to physiological stimuli.

Effects of gender on the central actions of neuropeptide Y and norepinephrine on vasopressin and blood pressure in the rat

Neuropeptide Y (NPY) and norepinephrine are co-localized in the noradrenergic projection from the A 1 nucleus of the medulla to the vasopressinergic magnocellular neurons of the supraoptic and paraventricular nuclei. Because this pathway is involved in the control of vasopressin release, we have examined the possibility that NPY and norepinephrine interact in this control. Because the stimulation of vasopressin release by the intracerebroventricular (i.c.v.) administration of norepinephrine is greater in male than in female rats, the experiments were carried out in conscious male rats and in female rats in the proestrous and non-proestrous phases of the estrous cycle. NPY (940 pmol i.c.v.) caused small sustained increases in plasma vasopressin concentrations that were greater in proestrous than in non-proestrous females and males. Norepinephrine i.c.v. increased plasma vasopressin levels transiently and to a greater extent in females than males. When NPY and norepinephrine were given together, the pattern of the vasopressin response was similar to that of norepinephrine alone. The magnitude of this response in males and proestrous females did not differ from that to norepinephrine alone; in non-proestrous females the response was twice that to norepinephrine alone. In non-proestrous rats, NPY also enhanced the pressor response to norepinephrine. Thus, NPY interacts centrally with norepinephrine in vasopressin release and cardiovascular function and this effect is dependent upon gender and phase of the estrous cycle.

Down-regulation of vasopressin V1a receptor mRNA in diabetes mellitus in the rat.

1. To investigate the mechanism of hepatic V1a vasopressin receptor down-regulation in streptozotocin-induced diabetes mellitus in the rat, we measured hepatic V1a receptor mRNA by in situ hybridization histochemistry using oligonucleotide probes to the V1a receptor and Northern blotting. 2. Diabetes mellitus caused hyperglycaemia, hyperosmolality and increased plasma vasopressin concentrations (P < 0.01). Hepatocyte V1a receptor mRNA was reduced by 76% in diabetic rats (P < 0.01) and by 53% in insulin-treated diabetic rats (P < 0.01) versus control rats, in parallel with reduced V1a radioligand binding and vasopressin-stimulated inositol phosphates production. There was a similar decrease in hepatic V1a/18S mRNA density ratio in the diabetic and diabetic+insulin groups (both P < 0.05 versus control). 3. These findings suggest that altered V1a mRNA transcription is responsible for the reduced hepatic V1a receptor density in diabetes mellitus.

The CCK A receptor antagonist devazepide inhibits the effect of apomorphine on vasopressin release in pigs

1. 1. A transient increase in plasma vasopressin concentrations represents a physiological correlate of nausea in animals that vomit. 2. 2. The CCK A receptor antagonist devazepide has previously been shown to inhibit vasopressin release induced in pigs by intravenous (i.v.) CCK. 3. 3. This study investigated whether devazepide (70 μg/kg i.v.) would affect vasopressin secretion induced in pigs ( n = 6) by the emetic drug apomorphine (25 μg/kg i.v.). 4. 4. Apomorphine stimulated vasopressin release in the 30 min period following injection; this effect was prevented by prior administration of devazepide. 5. 5. The results suggest that CCK A receptor antagonists may have the ability to prevent nausea and/or emesis.

Neuroendocrine and clinical effects of electroconvulsive therapy and their relationship to treatment outcome

Two groups of variables, endocrine and clinical, have been reported to have predictive value in determining response to electroconvulsive therapy (ECT) in depressed patients. Baseline levels of oxytocin associated neurophysin (OAN) and peak OAN response to ECT may predict clinical outcome, while the presence of delusional symptoms may indicate favourable initial response to ECT. The purpose of this study was to examine the relationship between these variables on initial and longer term response over a course of ECT, using a direct measure of plasma oxytocin concentrations. A substantial and immediate increase in oxytocin was seen after the first ECT, with significantly attenuated responses after the third and fifth ECTs. Increased plasma vasopressin concentrations were seen after all ECT treatments, each response being of similar magnitude. No associations were found between either endocrine baseline levels or peak responses, and clinical outcome. Only clinical variables predicted outcome, as patients with psychotic symptoms had more rapid initial response to ECT, and patients who had relapsed 2 months after the end of ECT had significantly higher depression ratings at day 14 of treatment than treatment responders.

Effects of relaxin on blood pressure and the release of vasopressin and oxytocin in anesthetized rats during pregnancy and lactation.

The effects of porcine relaxin (pRXN) on arterial blood pressure and on the release of vasopressin (VP) and oxytocin (OT) were investigated in urethane-anesthetized rats at different stages of pregnancy and lactation. Acute i.v. pRXN (5 micrograms) caused a significant increase in systolic and diastolic blood pressure in pregnant and lactating rats. However, the pressor response was attenuated from Day 14 of pregnancy to Day 1 of lactation. The hormone had no effect on blood pressure in Day 16, Day 19, or Day 21 pregnant rats. At all stages of pregnancy and lactation, i.v. pRXN caused a significant increase in plasma VP concentrations. This response was attenuated in Day 19 and Day 21 pregnant and in Day 1 lactating rats. Intravenous pRXN also caused a significant, short-term increase in plasma OT in pregnant and lactating rats. The OT response to pRXN was attenuated on Day 16 of pregnancy, and pRXN had no effect on plasma OT in late-pregnant rats. The data in this study demonstrate that pRXN causes an increase in both arterial blood pressure and VP and OT release in anesthetized pregnant and lactating rats. However, these effects are either reduced or not observed in late-pregnant and early-lactating rats.

Effect of inhibition of nitric oxide synthesis on vasopressin secretion in conscious rabbits.

NO synthase is present in magnocellular neurons of supraoptic and paraventricular nuclei as well as in the posterior pituitary gland and may participate in control of vasopressin secretion. To test this possibility, experiments were performed in conscious, chronically prepared rabbits to determine the effect of NO synthesis inhibition with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on basal vasopressin secretion and vasopressin responses to increased plasma osmolality (hypertonic saline infusion; P osm) and decreased blood pressure (nitroprusside infusion). L-NAME infusion (0.5 mg.kg-1 x min-1 i.v.) increased mean arterial pressure [MAP; 82.6 +/- 3.4 to 93.0 +/- 3.0 mmHg (P < 0.02)], decreased heart rate [HR; 242 +/- 12 to 209 +/- 9 beats/min (P < 0.02)], decreased plasma renin activity [PRA; 3.1 +/- 0.6 to 2.0 +/- 0.6 ng.ml-.2 h-1 (P < 0.001)], and increased plasma vasopressin concentration [P AVP; 2.2 +/- 0.3 to 4.5 +/- 1.0 pg/ml (P < 0.05)]. P(osm) did not change. Hypertonic saline infusion did not change MAP or HR but decreased PRA [4.3 +/- 0.8 to 0.9 +/- 0.2 ng.ml-1 x 2 h-1 (P < 0.01)], increased P(osm) [284 +/- 1 to 305 +/- 2 mosmol/kg H2O (P < 0.001)], and increased PAVP [2.8 +/- 0.3 to 12.7 +/- 2.7 pg/ml (P < 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)