Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vasopressin is the primary physiological factor regulating renal water reabsorption in mammals. Inhibitors of vasopressin-stimulated water reabsorption have previously been used as water diuretic agents in both experimental animals and man. The present studies describe and characterize the pharmacological effects of the potent vasopressin antagonist desGly d(CH2)5D-Tyr(Et)VAVP (SK&F 101926) and related analogs on renal water and solute excretion in conscious rats. Administration of SK&F 101926 was associated with dose-dependent increases in renal water excretion in conscious hydropenic rats. A selective vasopressin pressor (V1) antagonist (SK&F 100273) was inactive as a diuretic agent in these tests. SK&F 101926 antagonized, in a competitive fashion, exogenous vasopressin-stimulated antidiuresis in conscious water-loaded rats. Only modest increases in renal excretion of Na+, K+, and urea were observed when SK&F 101926 was administered. No changes in endogenous creatinine excretion were associated with the administration of SK&F 101926, suggesting that this drug does not affect glomerular filtration rate. The rank order of bioequivalency of alternative routes of administration of SK&F 101926 was intraperitoneal = intravenous = intramuscular = subcutaneous greater than intranasal much greater than rectal, ocular, and oral. SK&F 101926 (20 micrograms/kg/day) was effective in blocking the development of hyponatremia in a rat model of the syndrome of inappropriate antidiuretic hormone (SIADH). SK&F 100273 (100 micrograms/kg) hastened the onset of endotoxin-associated shock in rats. We conclude that SK&F 101926 is a potent water diuretic (aquaretic) agent in rats. The mechanism of action is most probably antagonism of vasopressin at renal epithelial (V2) receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1986
PMID:Discovery and therapeutic utility of vasopressin antagonists in rats. 243 70

Anesthetized rats of different strains show a hypotensive response to administration of an antagonist of the V1 receptors for vasopressin [d(CH2)5DAVP]. Such an effect is not seen in conscious, water-replete animals or in Long-Evans rats challenged with a subcutaneous injection of polyethylene glycol (PEG) to cause isosmotic hypovolemia. However, Long-Evans rats experiencing a similar volume reduction due to water deprivation show hyperosmolality and exhibit a small hypotensive response to d(CH2)5DAVP. Inhibition of the renin-angiotensin system following administration of d(CH2)5DAVP causes a greater hypotension in PEG-treated than in water-deprived Long-Evans rats. In both experimental conditions, the fall in blood pressure is greater than when captopril administration precedes that of d(CH2)5DAVP, indicating that prolonged administration of d(CH2)5DAVP may be interfering with mechanisms other than those mediated by peripheral V1 receptors. However, administration of d(CH2)5DAVP and captopril to water-deprived Long-Evans rats rarely causes the profound hypotension seen in water-deprived Brattleboro rats given captopril alone. In some adrenalectomized Wistar rats, following withdrawal of salt supplementation, the hypotensive response to d(CH2)5DAVP is the greatest seen in any experimental model. These results indicate that AVP is overtly involved in the support of blood pressure in various hypotensive states and, more importantly, may be responsible for the maintenance of a "normal" blood pressure in some conditions. However, the involvement of AVP in cardiovascular regulation in the majority of normotensive conditions is intriguingly subtle.
J Cardiovasc Pharmacol 1986
PMID:Vasopressin and the cardiovascular system: physiology or pharmacology? 243 71

The response to activation of specific receptors by arginine-vasopressin (AVP) has been studied in two cell models. In rat aortic smooth muscle cells in monolayer culture, the response of cytosolic free calcium ([Ca2+]i) upon addition of various agonists or antagonists was examined using the fluorescent calcium probe Quin 2. Activation of the vasopressin (V1) subtype of receptor resulted in a transient rise of [Ca2+]i, which could be prevented by a selective V1 antagonist but not by the calcium channel blocker, nifedipine and that was only slightly reduced in the absence of calcium in the medium. Release of 6-keto-prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin, was also observed in response to AVP. We conclude that one of the primary intracellular events following activation of V1 receptors on smooth muscle cells is a rise of [Ca2+]i released from intracellular stores, which mediates smooth muscle contraction and prostacyclin production. In superfused rat renal medullary tubular cells, the study of the release of cyclic AMP (cAMP) and prostaglandin E2 (PGE2) upon stimulation by AVP and various analogs (agonists or antagonists) permitted demonstration of the presence of two subtypes of receptors. The V2 type appeared to be linked to adenylate cyclase and was responsible for cAMP release, mediating the hydroosmotic effect of AVP, whereas the V1 type was related to calcium, mediating the prostaglandin production.
J Cardiovasc Pharmacol 1986
PMID:Effects of vasopressin and its analogs on rat aortic smooth muscle and renal medullary tubular cells: characterization of receptor subtypes. 243 72

The role of vasopressin in the kidney has classically been considered to result from its ability to increase water permeability in the collecting duct. Recent data, however, suggest that the hormone may also promote urinary concentration by increasing interstitial tonicity. The mechanisms whereby vasopressin could enhance interstitial tonicity include increasing urea permeability in the inner medullary collecting tubule, stimulation of solute reabsorption in the thick ascending limb of the loop of Henle, increasing the glomerular filtration rate of juxtamedullary nephrons, and decreasing vasa recta blood flow. We review experiments directed at assessing the role of vasopressin in these four processes. The multitude of effects of vasopressin appears to be well integrated and contributes to the tightly regulated urinary concentration mechanisms.
J Cardiovasc Pharmacol 1986
PMID:Vasopressin and the concentrating mechanism. 243 73

Chronic i.v. administration of a competitive antagonist of arginine-vasopressin (AVP), d(CH2)5-D-Tyr(Et)-VAVP, in Sprague-Dawley rats induced only a transient diabetes insipidus (DI)-like state. Water excretion and intake were markedly increased on the first day of administration but subsequently reverted to normal. A similar response to the antagonist was observed upon continuous i.v. infusion in Brattleboro rats, homozygous for hereditary hypothalamic DI, which had been substituted with exogenous AVP. This excludes the possibility that increased secretion of endogenous AVP had overcome the blocking effect of the competitive antagonist in Sprague-Dawley rats. However, when AVP was withdrawn from chronically AVP-treated DI rats, water intake increased to values higher than those observed after the antagonist. Subsequently, water intake also decreased but remained elevated compared to that of AVP-substituted rats receiving the antagonist. This suggests that the antagonist might have AVP-like agonistic properties that limit its efficacy and allow compensatory mechanisms to restore normal water balance despite continuous blockade of AVP receptors. The agonistic properties of d(CH2)5-D-Tyr(Et)VAVP were verified upon chronic i.v. administration in nonpretreated DI rats. Thus, the normalization of water balance in Sprague-Dawley rats chronically receiving d(CH2)5-D-Tyr(Et)VAVP is probably due to the activation of compensatory mechanisms and to the agonistic effects of d(CH2)5-D-Tyr(Et)VAVP.
J Cardiovasc Pharmacol 1986
PMID:Chronic blockade of vasopressin receptors in rats. 243 74

We first discuss the question of direct versus indirect mechanisms in the vasoconstrictor effects induced by low plasma levels of arginine vasopressin (AVP). By infusing AVP directly into the arteries supplying various organs and tissues and measuring regional blood flows with radioactive microspheres in conscious dogs, it was determined that the increase in resistance measured after systemic administration of small amounts of AVP in the skeletal muscle, small intestine, colon, and abdominal fat results in large part from indirect mechanisms. Direct vasoconstrictor effects of AVP at these plasma concentrations were limited to the skin, the pancreas, and the compact bones. We then consider the question of cardiovascular effects of AVP from its antidiuretic activity. In the presence of a vascular antagonist, AVP decreased peripheral resistance and increased cardiac output in conscious dogs. An analog with selective antidiuretic activity, VDAVP, produced the same effects as the combination of vasopressin plus vascular antagonist. These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposed to many of those produced by its vasoconstrictor action. Studies in 48-h dehydrated dogs showed that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin under these conditions is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine vasopressin molecule.
J Cardiovasc Pharmacol 1986
PMID:Cardiovascular effects of vasopressin: some recent aspects. 243 75

Three groups of dogs were studied to determine to what extent the suppression of plasma renin activity (PRA), natriuresis, and hyponatremia, seen with chronic elevations of plasma vasopressin (AVP), were caused by volume expansion or some other more direct actions of AVP. The dogs of group 1 (n = 7) were infused with AVP (0.36 ng/kg/min, i.v.) for 2 weeks, while water intake was maintained at a constant level. The dogs of group 2 (n = 6) were permitted to drink ad libitum during AVP infusion. The dogs of group 3 (n = 7) were infused with AVP while total body weight and volume were maintained at a constant level by use of an electronically servocontrolled water infusion system. Group 1, with fixed water intake, retained a large fluid volume (1.4 L), with an associated 36 mm Hg rise in mean arterial blood pressure (MAP). Associated with this hypertension and increased volume were a suppression of PRA and substantial decreases in plasma sodium concentration with increased excretion of sodium. With ad libitum drinking (group 2), only mild volume expansion occurred, with no significant elevations of MAP or changes in sodium excretion. With a volume expansion of 300-400 ml, there was a significant decrease of PRA and plasma sodium concentration. Group 3, servocontrolled dogs, exhibited no change in MAP, plasma sodium concentration, or PRA throughout the 2-week period of AVP infusion. Sodium excretion was mildly elevated only on the first day of AVP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1986
PMID:Vasopressin excess: relative contribution of volume retention versus direct actions on renin secretion and sodium excretion. 243 76

Lesions of the brain region surrounding the anteroventral third ventricle (AV3V) have been shown to result in adipsia without a corresponding antidiuretic response or rise in plasma vasopressin levels. Electron microscopic examination of the supraoptic nucleus and neural lobe of the pituitary has shown that large stores of neurosecretory material build up in the neurohypophysis. In the present study, the increased neurosecretory material was characterized by immunocytochemistry. Vasopressin immunoreactivity was examined and compared between adipsic rats with AV3V lesions, water-deprived rats, and normal rats. Two days after surgery, sham-lesioned, water-deprived rats displayed decreased vasopressin immunostaining density compared to normal controls, and adipsic AV3V-lesioned rats displayed increased vasopressin immunoreactivity throughout the magnocellular-hypophyseal system. These results indicate that AV3V lesions interrupt neural inputs that stimulate the magnocellular system to release vasopressin in response to normal humoral stimuli.
J Cardiovasc Pharmacol 1986
PMID:Changes in magnocellular-neurohypophyseal vasopressin following anteroventral third-ventricle (AV3V) lesions. 243 77

Using techniques of intracerebroventricular administration of vasopressin, microinjection of vasopressin into specific brain nuclei, electrical stimulation, and ablation of specific nuclei, we found that vasopressin, through an effect on central neural structures, increases mean arterial pressure and heart rate via an increase in sympathetic outflow and that deoxycorticosterone acetate (DOCA)-salt hypertensive rats show increased sensitivity and responsiveness to the central effects of vasopressin. Furthermore, we found that an important central target area for the cardiovascular effects of vasopressin is the pontine nucleus locus coeruleus. Ablation of the locus coeruleus markedly attenuates the cardiovascular effects of vasopressin as well as the development of DOCA-salt hypertension. Taken together, our results suggest a link between vasopressin, the locus coeruleus, and the sympathetic nervous system in normal cardiovascular regulation as well as in the pathogenesis of DOCA-salt hypertension. Our studies support the hypothesis that vasopressin modifies sympathetic drive through an action on central neural target areas, such as the locus coeruleus controlling sympathetic outflow. Our data further suggests that vasopressin may participate in the pathogenesis of DOCA-salt hypertension by inducing stimulation of the sympathetic nervous system at the region of the locus coeruleus in this model.
J Cardiovasc Pharmacol 1986
PMID:Role of central vasopressin in cardiovascular regulation. 243 78

Vasopressin secretion is stimulated by hyperosmolality, hypovolemia, or hypotension and is inhibited by hypoosmolality, hypervolemia, or hypertension. These osmotic and hemodynamic influences are mediated by neuronal afferents that originate in separate osmoreceptors or baroreceptors but ultimately converge to act on the same neurosecretory neurons. Functionally, the two control systems are integrated in such a way that osmoregulation is altered but not disrupted by hemodynamic influences. In patients with uncomplicated essential hypertension, basal as well as osmotically stimulated vasopressin is completely normal. The vasopressin response to an acute reduction in blood pressure is also normal if the values are expressed relative to the change in pressure. However, if the plasma vasopressin response is plotted as a function of absolute blood pressure, the line describing the relationship lies well to the right of normal. Thus, although it is completely intact, the baroregulatory mechanism appears to be reset to a higher level in essential hypertension. These results suggest that increased secretion of vasopressin does not contribute to the genesis or maintenance of uncomplicated, untreated essential hypertension but may antagonize the therapeutic effect of some antihypertensive drugs. If so, antagonists of V1 receptors may be useful as second-line adjunctive therapy for this condition.
J Cardiovasc Pharmacol 1986
PMID:Osmoregulation and baroregulation of plasma vasopressin in essential hypertension. 243 80


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