Increased Plasma Vasopressin Research Articles

Increased Plasma Vasopressin and Serum Uric Acid in the Low Renin Type of Essential Hypertension

In 22 50-year-old men with long-standing, untreated essential hypertension of the low renin type, venous plasma vasopressin concentrations were about three times those of 15 matched normotensive control subjects (p less than 0.005). These patients also had increased arterial concentrations of noradrenaline and adrenaline (p less than 0.05) but there was no direct association between these two catecholamines and vasopressin. On the other hand, adrenergic beta-receptor blockade with oxprenolol reduced both blood pressure and plasma vasopressin (p less than 0.01) while venous plasma dopamine concentrations significantly increased. In addition, the hypertensives had highly significantly increased serum uric acid (p less than 0.001) that correlated positively with venous vasopressin concentrations (p less than 0.05). According to these data, patients with the volume-sustained low renin type of essential hypertension have increased plasma vasopressin concentrations that probably are inversely related to dopaminergic nervous activity. The data also indicate that increased plasma vasopressin correlates with serum uric acid, most probably through increased tubular reabsorption of this acid.

Cardiovascular response to vasopressin vasopressor antagonist administration during water deprivation in the rat.

The cardiovascular effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injection of a selective vasopressin vasopressor antagonist, [1-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid-2-(0-methyl)tyrosine]arginine vasopressin (TMe-AVP) were examined in conscious rats under basal conditions and following 48 h of water deprivation. Pressor responses to i.v. vasopressin (50 ng/kg) were not blunted by i.c.v. treatment with either vehicle or 0.5 microgram/kg TMe-AVP. A dose of 5.0 microgram/kg TMe-AVP (i.c.v.) did reduce the pressor response to vasopressin, indicating peripheral leakage of the antagonist. Water deprivation for 48 h increased plasma vasopressin concentrations from 0.7 +/- 0.1 to 2.8 +/- 0.1 microU/ml and increased blood pressure from 112 +/- 2 to 123 +/- 1 mm Hg. No effect of the vasopressin antagonist on blood pressure could be detected following either i.c.v. (0.5 microgram/kg) or i.v. (5.0 micrograms/kg) treatment in water-deprived animals. However, a significant increase in heart rate was observed in water-deprived rats following i.v. injection of 5.0 micrograms/kg of TMe-AVP. Central vasopressin vasopressor receptor blockade appears to exert little effect on blood pressure either under basal conditions or during water deprivation. The data further delineate the relationship of plasma vasopressin concentrations to cardiovascular homeostasis.

Homeostatic responses to water deprivation or hemorrhage in lactating and non-lactating bedouin goats

1. 1. Three lactating and three non-lactating black Bedouin goats were subjected to four days of water deprivation or to hemorrhage. 2. 2. Four days of water deprivation caused body wt losses of 32 and 23% and plasma volume losses of 30 and 34% in lactating and non-lactating goats respectively. 3. 3.Plasma osmolality increased 17 and 15% in lactating and non-lactating goats. Plasma arginine vasopressin concentration rose from about 5 pg/ml to a mean of 36 pg/ml. Plasma renin activity increased from about 0.7 ng/ml/hr to a mean of 3.45 ng/ml/hr in lactating and to 3.15 ng/ml/hr in non-lactating goats. 4. 4. At 4.5 hr post-rehydration plasma osmolality and plasma vasopressin concentration were back to normal in non-lactating, but still elevated in lactating goats. Plasma renin activity increased after rehydration. 5. 5. Rapid blood volume loss of 21–28% increased plasma vasopressin concentration to 16–35 pg/ml in non-lactating and to 70 or > 500 pg/ml in lactating goats. 6. 6. It is concluded that black Bedouin goats are well adapted to endure severe dehydration and rapid rehydration, but that they (especially lactating animals) react strongly to rapid volume depletion.

Circulatory and humoral responses of sympathectomized fetal sheep to hypoxemia.

In fetal sheep, hypoxemia causes arterial hypertension, bradycardia, a redistribution of blood flow, and an increase in plasma vasopressin and catecholamine concentrations. To assess the role of the sympathetic nervous system in mediating these responses, we administered 6-hydroxydopamine to 11 chronically catheterized fetal sheep. Some of the responses to acute hypoxemia, achieved by administration of a low-O2 gas mixture to the ewe, were similar to those in intact fetal sheep. Fetal arterial O2 tension decreased from 22 +/- 3 to 12 +/- 3 (SD) Torr; fetal heart rate decreased transiently; combined ventricular output and umbilical-placental blood flow, as measured by the radionuclide-labeled microsphere technique, were maintained; cerebral, myocardial, and adrenal blood flow increased, and pulmonary blood flow decreased. However, there was no significant change in arterial pressure or blood flow to the peripheral, renal, and splanchnic circulations in the chemically sympathectomized fetuses in response to hypoxemia. The sympathetic nervous system is important in certain fetal vascular responses to hypoxemia but is not necessary for vascular responses in certain critical organs and thus is not crucial for fetal survival during hypoxia.

Central cardiovascular effects of mammalian neurohypophyseal peptides in conscious rats

To confirm and extend the results of previous studies which demonstrated central cardiovascular effects of vasopressin in anesthetized rats, we determined blood pressure and heart rate changes for 30 minutes after intracerebroventricular injections of arginine vasopressin, arginine vasotocin and oxytocin in conscious rats. As compared to sham injections, significantly greater increases in either systolic or diastolic blood pressure were noted over the 30 minutes which followed the injection of 0.15, 1.0 or 10.0 nM of either vasopressin or vasotocin. In animals given vasopressin, plasma levels of the peptide were determined. There was a substantial increase in plasma vasopressin only after the highest dose. Overall blood pressure responses to doses of oxytocin as high as 100 nM were not significantly different than sham injections. Heart rate following both vasopressin and vasotocin was increased at 0.15 nM, was initially decreased then increased at 1.0 nM and was substantially decreased after the 10.0 nM dose. There was a significant increase in heart rate at the 10.0 nM and 100 nM doses of oxytocin. Dose response curves for systolic blood pressure and heart rate 20 minutes after injection were similar for vasopressin and vasotocin. We conclude that arginine vasopressin has significant central pressor and tachycardic effects in conscious rats, and it is related, at least in part, to the tail structure of the peptide, which is shared with arginine vasotocin.

Osmoregulation of thirst and vasopressin secretion in human subjects: effect of various solutes.

Various hypertonic solutions were infused in healthy human volunteers to determine their effect on thirst and vasopressin secretion. Hypertonic saline and mannitol produced prompt and parallel increases in plasma osmolality and vasopressin concentration. For both of these solutes, there was a high degree of correlation between these measurements. The slope describing this relationship varied considerably between individuals, but the same subjects showed similar slopes with either saline or mannitol. Both solutions stimulated thirst. Hypertonic urea infusions produced a comparable rise in osmolality but produced a smaller increase in plasma vasopressin and stimulated thirst in only one of the subjects. With urea, the correlation between plasma osmolality and vasopressin was significantly lower. Within individuals, the slope describing this relationship was significantly correlated with that seen during hypertonic saline. Hypertonic glucose significantly increased plasma osmolality but decreased plasma vasopressin and had no detectable effect on thirst. We conclude that osmoregulation of vasopressin in humans is mediated by a selective osmoreceptor that is located primarily outside of the blood-brain barrier and that individual differences in osmoregulatory sensitivity are not solute specific.

Effects of nonhypotensive hemorrhage on renal organ and urinary clearances of vasopressin in the dog.

A study was undertaken to investigate the effects of moderate nonhypotensive hemorrhage on the renal organ and urinary clearances of vasopressin in anesthetized dogs. A nonhypotensive hemorrhage was conducted in nine dogs by withdrawal of 12 ml/kg arterial blood over 10 min. This reduction in blood volume increased the plasma vasopressin concentration from a prehemorrhage value of 4.3 +/- 0.5 to 12.5 +/- 3.4 microU/ml (P less than 0.01) in the 15-min period immediately after hemorrhage and to 8.1 +/- 1.4 microU/ml (P less than 0.01) in the 45- to 60-min period after hemorrhage. The increased plasma vasopressin concentration was not associated with changes in either plasma osmolality or mean arterial blood pressure. The urinary excretion of vasopressin increased significantly after hemorrhage (P less than 0.01, 0-15 min after hemorrhage; P less than 0.05, 45-60 min after hemorrhage) and correlated significantly with the plasma vasopressin concentration (r = 0.92; P less than 0.001). However, this moderate nonhypotensive hemorrhage did not change the renal vasopressin extraction ratio or the renal organ and urinary clearances of vasopressin from their prehemorrhage values of 0.27 +/- 0.02, 2.00 +/- 0.20 ml/min X kg, and 1.43 +/- 0.13 ml/min X kg, respectively. At no time were these values different from those in nine time control dogs. Thus, changes in the renal handling of vasopressin do not contribute to the increase in the plasma vasopressin concentration after moderate nonhypotensive hemorrhage.

Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs.

To better understand the role of arginine vasopressin in cardiovascular regulation, we measured in unanesthetized dogs regional blood flows with radioactive microspheres before and during 1-h vasopressin infusions that increased the vasopressin concentration of plasma by 11 +/- 0.6 pg/ml. Cardiac output measured by an electromagnetic flowmeter decreased by 13%. Blood flows to the skeletal muscle and skin, the areas most affected, decreased by 30.8 and 34.3%, respectively. In the same group of dogs a period of 48-h water restriction increased plasma vasopressin by 6.9 +/- 1.3 pg/ml and reduced cardiac output by 14.4%. Skeletal muscle blood flow decreased by 32.8%, a pattern strikingly similar to that following vasopressin infusion. Obvious differences between vasopressin infusion and dehydration were also noted, in particular in the skin and splanchnic areas. However, the possibility that vasopressin contributed to the cardiovascular adjustments to dehydration must be considered. The use of an antagonist of the vascular effects of vasopressin, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]arginine-vasopressin ([dPTyr(Me)]AVP), did not permit us to clarify this issue, because this analogue given alone exerted pronounced systemic and regional cardiovascular effects that resembled those of vasopressin.

Orthostatic fluid-electrolyte and endocrine responses in fainters and nonfainters.

A tilt-table test was administered to five young men before (test 1) and after (test 2) 8 days of heat acclimation (2-h daily exercise at 50% VO2max at 40 degrees db, 30 degrees C wb) and to five other young men before and after the same exercise at 24 degrees C to determine fluid-electrolyte and endocrine responses in orthostasis in fainters and nonfainters. Half of the 10 subjects showed improved orthostatic reactions from test 1 to test 2 (disappearance of nausea and dizziness and improved heart rate and blood pressure), and the other 5 subjects showed no improvement. The improvement, especially in the nonfainters, was related to increases in posttilt plasma volume (PV) and plasma concentration of potassium. During test 1, plasma renin activity (PRA) increased five times from supine to orthostatis, with a corresponding increase in plasma vasopressin (ADH) of 50 times. The corresponding increases in test 2 were lower by 50 and 75% compared with those occurring in test 1 for PRA and ADH, respectively. PRA was five times higher in nonfainters than in fainters in test 1, whereas ADH showed an opposite trend. The orthostatic-induced increase in ADH seems to be related to volume control independent of PRA. This increase is reduced with improvement in orthostatic reactions, probably because of an increase in PV.

Effect of intracerebroventricular captopril on vasopressin and blood pressure in spontaneously hypertensive rats.

In conscious, unrestrained spontaneously hypertensive rats (SHR), mean arterial blood pressure (MAP) increased from a pretreatment value of 150 +/- 4 to 179 +/- 7mm Hg within 10 min (p less than 0.01) following an intracerebroventricular (i.c.v.) injection of captopril (2 mg/kg body weight), and the plasma vasopressin concentration was increased eightfold (p less than 0.01). MAP than fell to 131 +/- 5 mm Hg at 120 minutes (p less than 0.01), and plasma vasopressin concentration returned to pretreatment levels. The initial increase in MAP was due in large part to increased plasma vasopressin levels since this increase was reduced 50% by pre-treatment with a specific antagonist of the pressor action of vasopressin. The reduction in MAP at 120 minutes in captopril-treated rats may been nonspecific, since a similar effect was observed in SHR given an i.c.v. injection of a control solution. In (Wistar-Kyoto) WKY rats, i.c.v. captopril was without a statistically significant effect on MAP, but the plasma vasopressin concentration increased three-fold (p less than 0.01). These findings may reflect an increased sensitivity of the control system for vasopressin release in the SHR.

Insulin-Induced Hypoglycemia in Conscious Dogs. I. Dose-Related Pituitary and Adrenal Responses*

We have measured changes in plasma glucose, ACTH, corticosteroids, and vasopressin and hematocrit after five doses of insulin in six conscious dogs. We found insulin dose-related changes for each of these responses (P less than 0.01, by two-way analysis of variance). The increases in plasma ACTH and hematocrit correlated to the decrease in plasma glucose; the increase in plasma vasopressin was more strongly correlated with the increases in plasma Na+ than with the decreases in plasma glucose. Each dog appeared to have a characteristic ACTH response curve; therefore, the relationship between plasma glucose and plasma ACTH responses varied among dogs, but was significant in five of six dogs studied. Maximal plasma corticosteroid responses occurred with submaximal plasma ACTH responses (200-600 pg/ml). A single dose of insulin produced reproducible changes in plasma ACTH when given to five dogs in three separate experiments over a 2- to 6-month period. In these experiments, the measurement of ACTH allowed us to distinguish three levels of response to insulin, whereas measurement of the corticosteroid response allowed us to distinguish only two levels of response.

Effects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chloride

Intracerebroventricular (i.v.t.) administration of β-endorphin or leucine 5-enkephalin inhibited drinking behavior, the pressor response and increased plasma vasopressin concentration stimulated by an acute elevation in CSF sodium chloride concentration (10 μl, 1 M NaCl i.v.t.). These effects of endogenous opioid peptides were prevented by naloxone, indicating opiate receptors were required for the biologic response. Drinking behavior associated with regulatory stimuli operant during dehydration was also inhibited by opioid peptides. β-Endorphin (i.v.t.) delayed the onset and/or reduced the volume of water consumed in response to hypertonic sodium chloride (relative cellular dehydration), polyethylene glycol (hypovolemia) and food-associated drinking behavior. Inhibition of drinking did not appear related to sensory-motor dysfunction as another motivated behavior, eating (onset, amount consumed) was unaffected by β-endorphin. It is concluded from these results that centrally administered endogenous opioid peptides inhibit sodium chloride-stimulated cerebral mechanisms affecting blood pressure and hydration.

Vasopressin function in familial cranial diabetes insipidus

A family suffering from cranial diabetes insipidus, that extends over 4 generations, is described. Inheritance of polyuria was autosomal dominant. Vasopressin function was studied in members of the last 2 generations, 4 of whom had polyuria. Osmoregulation of vasopressin secretion was assessed by infusion of hypertonic saline. Plasma vasopressin remained undetectable in one patient, while 2 others had very blunted vasopressin responses to osmotic stimulation. Three non-osmotic stimuli were applied. Controlled hypotension produced by trimetaphan infusion and insulin-induced hypoglycaemia did not increase plasma vasopressin but apomorphine-induced nausea caused a minimal rise in plasma vasopressin to 0.7 pg/ml. Polyuria and thirst resolved with antidiuretic therapy in all patients studied. Congenital absence of vasopressin as in Brattleboro rats is unlikely to account for diabetes insipidus in this disorder since small increases in vasopressin have been demonstrated in these patients. In view of previous post-mortem findings, familial cranial diabetes insipidus is most likely to be due to degeneration of vasopressin-synthesizing neurones.

Hemodynamic effects of exogenous and endogenous vasopressin at low plasma concentrations in conscious dogs.

The possibility that vasopressin plays a role in cardiovascular control arouses increasing interest. We studied in unanesthetized dogs the hemodynamic consequences of 1-hour vasopressin infusions that modified plasma concentrations over a range similar to that found in physiological situations. We also examined the cardiovascular events following the stimulation of endogenous vasopressin release by an increase in plasma osmolality. In dogs with baroreceptor reflexes intact, vasopressin infusions which increased plasma vasopressin concentration by 2-20 fmol/ml did not affect mean arterial pressure. However, they significantly decreased cardiac ouput (measured by an electromagnetic flowmeter) and increased total peripheral resistance. After baroreceptor denervation, vasopressin infusion rates as low as 40 fmol/kg per min (0.017 microU/kg per min) led to an increase in mean arterial pressure. Cardiac output was unaffected until much higher infusion rates were used. Changes in total peripheral resistance were very similar to those calculated in dogs with intact baroreceptors. The release of vasopressin following infusions of hypertonic solutions either intravenously or into a carotid artery induced detectable hemodynamic changes which appeared in many respects similar to those following low infusion rates of vasopressin. We conclude that physiological plasma concentrations of vasopressin have hemodynamic effects even though they do not normally modify arterial pressure, presumably because of some particular interaction of vasopressin with the baroreceptor reflex.

Influence of the emetic reflex on vasopressin release in man

The mechanisms underlying the frequent association of nausea and vomiting with elevations of plasma vasopressin(PAVP) were studied in man and rat. After oral water loads (N = 16), plasma osmolality fell in all human subjects and was associated with a decline in PAVP in 14 asymptomatic human subjects. In 2 human subjects, nausea occurred and was associated with increases in PAVP, without changes in blood pressure. During ethanol infusion (N = 28), PAVP was suppressed unless nausea supervened. In 4 nauseated human subjects, PAVP escaped from ethanol inhibition and rose to levels 10 times basal, despite the absence of hemodynamic changes. Apomorphine, a potent dopamine agonist and emetic agent, was administered to human volunteers in doses of 7 to 24 microgram/kg. There was no increase in PAVP in 3 human subjects who remained asymptomatic (7 to 16 microgram/kg). Ten human subjects experienced nausea after 16 microgram/kg, which was followed shortly by marked increases in PAVP. Emesis occurred in 5 human subjects given 16 to 24 microgram/kg, and was followed by PAVP levels similar to those seen with nausea alone. In 7 human subjects from the nausea group, the repeat study (16 microgram/kg) after pretreatment with dopamine antagonist (haloperidol, N = 4; fluphenazine, N = 3) resulted in complete blockage of apomorphine-induced AVP release. In rats, which lack an emetic reflex, apomorphine doses of 200 microgram/kg induced only slight increases in PAVP when compared to the response to 16 microgram/kg in man. These studies indicate that stimulation of the emetic reflex results in AVP-release in man. Nausea-mediated AVP release supervenes over concomitant osmolar or pharmacologic (ethanol) inhibition.

Centrally Mediated Hydration Effects of Angiotensin in Various States of Sodium Balance

Angiotensin, present in the central nervous system and kidneys, affects salt/water balance when administered to either site but the relationship between central and peripheral actions is unclear. One reported difference between central and peripheral administration of the peptide is that the former causes natriuresis whereas the latter conserves sodium. We injected angiotensin II into the lateral cerebroventricles of conscious rats maintained on low, normal and high sodium intakes. Prior to injection, plasma [Na⁺] and hematocrits were similar in the 3 groups. Angiotensin increased plasma vasopressin content in all groups at 1 and 5 min; the 1-min peak was greater in the high Na⁺ rats. In control and low Na⁺ rats plasma renin activity (PRA) was suppressed 5 and 20 min after angiotensin. Basal PRA of high Na⁺ rats was low and tended to be further suppressed by angiotensin. Angiotensin-induced water intake was similar in all groups. Thus, the response pattern to intraventricular angiotensin (vasopressin release, PRA suppression and drinking behavior) occurred over a range of sodium intakes sufficient to suppress or elevate basal PRA. These responses, and the natriuretic effect of intraventricular angiotensin, would be beneficial under conditions of Na⁺ excess. Conversely, these effects would be detrimental in Na⁺-defícient conditions since they reduce the ability to maintain extracellular [Na⁺]. Angiotensin effects in brain may be increased by sodium excess whereas the renal angiotensin system is utilized in response to Na⁺ deficiency.

Regulation of water intake.

Regulation of water intake.

Vasopressin release during nonhypotensive hemorrhage and angiotensin II infusion.

These experiments were designed to determine whether angiotensin II (AII) could potentiate the increase in plasma vasopressin (ADH) concentration produced by continuous, nonhypotensive hemorrhage in nephrectomized dogs. Infusion of AII (10 ng/kg.min) into a common carotid artery in nonbled dogs did not increase plasma ADH levels, suggesting that increases in carotid arterial plasma AII concentration alone do not stimulate an increase in ADH release. Subsequently, nephrectomized dogs subjected to nonhypotensive hemorrhage (0.44 ml/kg.min) were infused as follows: 0.9% saline intravenously, AII (10 ng/kg.min) intravenously, or AII (10 ng/kg.min) into the carotid. The Plasma ADH concentration increased in all three groups of dogs during hemorrhage. Although the AII-infused dogs demonstrated significant increases in plasma ADH levels earlier during hemorrhage, these changes were small; there were no statistically significant differences in plasma ADH concentrations among the three groups. These results suggest that increases in plasma AII concentration have little or no significant effect on the volume control of ADH release.

Angiotensin interaction with thirst mechanisms.

ARTICLESAngiotensin interaction with thirst mechanismsWB Severs, J Summy-Long, and A Daniels-SeversWB Severs, J Summy-Long, and A Daniels-SeversPublished Online:01 Feb 1974https://doi.org/10.1152/ajplegacy.1974.226.2.340MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByThe Neuroendocrinology, Neurochemistry and Molecular Biology of Thirst and Salt Appetite1 January 2007BibliographyAltered drinking responses in dogs with chronic metabolic alkalosisPeptides, Vol. 9Do peripheral and cerebroventricular injections of angiotensin II act at the same site? studies on additivity of drinkingBrain Research Bulletin, Vol. 16, No. 2Zur Pathogenese und Pathophysiologie der essentiellen HypertonieTwo inhibitors of angiotensin‐converting enzyme, enalapril and captopril, increase salt appetite of rats20 October 2009 | Journal of Toxicology and Environmental Health, Vol. 14, No. 5-6Renin activity in rat choroid plexi: effects of water-deprivation and hypovolemiaExperientia, Vol. 39, No. 4An Overview of Current Concepts Regarding the Pathogenesis and Pathophysiology of HypertensionEffects of centrally administered endogenous opioid peptides on drinking behavior, increased plasma vasopressin concentration and pressor response to hypertonic sodium chlorideBrain Research, Vol. 221, No. 2Hypotension and thirst in rats after phentolamine treatmentPhysiology & Behavior, Vol. 27, No. 3Renal effects of beta-adrenoceptor blockadeKidney International, Vol. 18, No. 5Effects of chronic intraventricular administration of angiotensin II on drinking behavior and blood pressurePharmacology Biochemistry and Behavior, Vol. 10, No. 1Consummatory behavior and urine production after cerebroventricular injection of vasopressin and vasopressin antiserumEuropean Journal of Pharmacology, Vol. 51, No. 4Peptides and the Central Nervous SystemSubfornical organ: Duration of dipsogenic action of angiotensin-IINeuroscience Letters, Vol. 5, No. 3-4Effects of angiotensin II on schedule dependent and induced behavior at recovered body weightPharmacology Biochemistry and Behavior, Vol. 6, No. 6DRINKING ELICITED BY ANGIOTENSIN OR HYPEROSMOTIC STIMULATION OF THE RAT ANTERO-VENTRAL THIRD VENTRICLE: SINGLE OR SEPARATE NEURAL SUBSTRATES?The physiological basis of thirstKidney International, Vol. 10, No. 1The role of angiotensin in thirstLife Sciences, Vol. 17, No. 10The Renin-Angiotensin System and Drinking BehaviorAngiotensin and thirst: Studies with a converting enzyme inhibitor and a receptor antagonistLife Sciences, Vol. 15, No. 3Angiotensin stimulation of the central nervous system More from this issue > Volume 226Issue 2February 1974Pages 340-344 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.226.2.340PubMed4359513History Published online 1 February 1974 Published in print 1 February 1974 Metrics

Third ventricular injection of hypertonic NaCl and natriuresis in cats.

Third ventricular injection of hypertonic NaCl and natriuresis in cats.