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

The hypothesis that withdrawal of increased sympathetic activity may be beneficial in heart failure was tested by administration of the centrally acting adrenergic inhibitor methyldopa. Fourteen subjects with chronic, stable New York Heart Association Functional Class 2 or 3 heart failure receiving digitalis and diuretics were randomized to methyldopa (n = 8) 500-1000 mg daily or placebo (n = 6). Clinical, hemodynamic, neurohumoral, and platelet alpha 2-receptor effects were studied after chronic (3 weeks) administration. Sympathetic inhibition did not alter symptom status or exercise duration but reduced plasma norepinephrine concentration during exercise and permitted the same level of exercise to be attained at a lower pressure-rate product, indicating reduced myocardial oxygen consumption. Left ventricular ejection fraction and stroke volume tended to increase, and systemic vascular resistance tended to decrease during exercise after methyldopa administration, suggesting enhanced vasodilation. Upright plasma renin activity increased from 8.2 +/- 2.2 to 13.3 +/- 3.0 ng/nl/h (p = 0.03) after methyldopa, but plasma antidiuretic hormone concentration changed insignificantly. In a subset of patients, platelet alpha 2-receptor density and affinity were unaltered. Renal function was also unchanged. Thus, sympathetic inhibition induced by methyldopa in selected patients with chronic, stable heart failure does not worsen symptom status or exercise performance, and may produce a beneficial effect by withdrawal of excess sympathetic activity with reduction of plasma norepinephrine levels.
J Cardiovasc Pharmacol
PMID:Sympathetic inhibition with methyldopa in heart failure. 242 85

When tripamide was added to the food of spontaneously hypertensive rats (SHR), there were no appreciable effects on heart rate, body weight, or food intake. Tail-cuff systolic pressures measured weekly were also unaffected in normotensive control rats (WKY), but the elevation expected in SHR was significantly reduced. Pressor responses to hypothalamic stimulation were also reduced selectively only in SHR. A peripheral inhibition of cardiovascular reactivity was considered unlikely, since pressor responses to injected norepinephrine, tyramine, or vasopressin were unaltered. Diminished pressor responsiveness was considered to be due to concurrent reduction of central sympathetic vasomotor activity, because sympathetic nerve responses to hypothalamic stimulation were appreciably lessened in tripamide-treated SHR. Although neither the site nor the mechanism causing sympathetic inhibition was determined exactly, our results are in accord with the interpretation that antihypertensive effects of tripamide in SHR depend, at least partly, on sympathetic inhibition.
J Cardiovasc Pharmacol
PMID:Antihypertensive and hypothalamic depressant effects of tripamide in spontaneously hypertensive rats. 242 91

The adenylate-cyclase activator forskolin, the guanylate-cyclase stimulator sodium nitroprusside, the phosphodiesterase inhibitor Ro 15-2041, different Ca-entry blockers, as well as various vasodilators, and the atrial natriuretic peptide were tested for antiplatelet activity. Thrombin, vasopressin, ADP, arachidonic acid, and the dihydropyridine Ca agonist CGP 28392 were used as platelet activators. The physiological and biochemical parameters of platelet function studied included shape-change reaction, intracellular free-Ca modulation, and cyclic nucleotide formation. When inhibition of the shape-change response occurred, it was accompanied by inhibition of the increase in intracellular free Ca. Furthermore, the results suggest a possible intracellular site of action of Ca entry blockers in platelets, and confirm the importance of modulation of cyclic nucleotides in the regulation of platelet function, regardless of the mechanism of platelet activation. Additional antiplatelet activity of antihypertensive agents may have a beneficial effect in reducing the associated risk of thrombo-embolic complications in essential hypertension.
J Cardiovasc Pharmacol 1986
PMID:Vasodilating agents and platelet function: intracellular free calcium concentration, cyclic nucleotides, and shape-change response. 243 9

At least two signal-generating systems are involved in the actions of various hormonal factors in human platelets--the adenylate cyclase system and the phosphoinositide-metabolizing pathway. The formation of cyclic AMP (cAMP) by the adenylate cyclase system--consisting of the catalyst itself, the Ns and Ni proteins, and various hormone receptors--is stimulated by prostaglandins and adenosine, and is inhibited by alpha 2-adrenergic agonists, ADP, vasopressin, platelet-activating factor, and thrombin. On the other hand, the formation of inositol trisphosphate and diacylglycerol by the phosphoinositide-metabolizing pathway is stimulated by some of the latter agents, particularly by thrombin. There are apparently several mutual interactions between these two signal-generating systems. On the one hand, increases in the level of cAMP inhibit the formation of inositol phosphates and diacylglycerol. It is presently unclear whether this inhibitory effect of cAMP is due to a direct action at the phospholipase C itself or to an indirect mechanism, for example, a depletion of the substrate of the enzyme. On the other hand, protein kinase C, which is activated by diacylglycerol, largely interferes with the adenylate cyclase system. This kinase, when activated by diacylglycerol or phorbol esters, apparently phosphorylates the guanine nucleotide-binding alpha-subunit of Ni, which results in an impairment or loss of the inhibitory hormonal signal transduction to the adenylate cyclase. Thus, available evidence indicates that the two signal-generating systems present in platelet membranes are not completely separated, and furthermore suggests that they may even be causally related to each other.
J Cardiovasc Pharmacol 1986
PMID:Interactions between the hormone-sensitive adenylate cyclase system and the phosphoinositide-metabolizing pathway in human platelets. 243 28

Experiments were designed to determine the role of the endothelial cells and the metabolism of arachidonic acid in anoxic contractions of isolated canine basilar arteries. Rings, with and without endothelium, of these arteries were suspended for isometric tension recording; anoxia was induced by switching the mixture gassing the organ chamber from 95% O2-5% CO2 to 95% N2-5% CO2. In rings with endothelium, anoxia evoked increases in tension under basal conditions and during contractions to 5-hydroxytryptamine, uridine triphosphate, prostaglandin F2 alpha, and high K+. Under control conditions, these anoxic contractions were not prevented by alpha-adrenergic and serotonergic antagonists, by apyrase, or by inhibitors of cyclooxygenase. Anoxia prevented endothelium-dependent relaxations evoked by vasopressin and thrombin. In rings without endothelium, anoxia caused increases in tension during contractions evoked by various agonists, and in unstimulated preparations after inhibition of cyclooxygenase. Anoxic contractions were abolished by calcium entry blockers. These observations suggest that anoxic contractions of isolated canine basilar artery can be explained by the release of endothelium-derived contracting factor(s) and the accelerated entry of calcium in the smooth muscle cells, which possibly results from a diversion of arachidonic acid from the cyclooxygenase to the lipoxygenase pathway.
J Cardiovasc Pharmacol 1986
PMID:Anoxic contractions in isolated canine cerebral arteries: contribution of endothelium-derived factors, metabolites of arachidonic acid, and calcium entry. 243 36

The effects of human alpha-natriuretic peptide (alpha-ANP) were investigated in seven patients with severe congestive heart failure by incremental bolus injections and by a continuous infusion for 30 min. alpha-ANP was measured in plasma before and after administration. We found a significant inverse correlation between basal levels of alpha-ANP and cardiac output. The administration of alpha-ANP resulted in a fall of peripheral vascular resistance, an increase in cardiac output, a relatively small decrease in blood pressure, and almost no change in pulmonary arterial pressure. alpha-ANP inhibits aldosterone and cortisol secretion and enhances diuresis and urinary sodium and potassium excretion. Plasma adrenocorticotropic hormone was reduced in two of the patients after the continuous infusion. Plasma renin concentration, norepinephrine, vasopressin, and plasma levels of 6-keto prostaglandin F1-alpha and prostaglandin E2 were unchanged. A small but significant decrease of serum potassium was observed.
J Cardiovasc Pharmacol
PMID:Human atrial natriuretic peptide: plasma levels, hemodynamic, hormonal, and renal effects in patients with severe congestive heart failure. 243 34

The role of vasopressin in human hypertension was examined in a series of studies. In patients with primary hyperaldosteronism and benign essential hypertension, circulating vasopressin was generally lower than in normotensive subjects. In contrast, plasma vasopressin was increased (p less than 0.001) in patients with malignant-phase hypertension. However, compared to infused vasopressin in normal subjects, when plasma levels of up to 120 pg/ml did not affect blood pressure, the increased levels found in malignant hypertension could not account for the hypertension. The possibility that there may be an increased pressor sensitivity to vasopressin in hypertension was examined by infusing the peptide into nine patients with essential hypertension. This showed a slight increase in sensitivity compared to normotensive subjects, but again this was insufficient to account for the discrepancy between the circulating level of vasopressin and the extent of the raised blood pressure in the hypertensive patients. The effect of chronically elevated levels of vasopressin was studied in a group of patients with the syndrome of inappropriate ADH excess as a consequence of bronchogenic carcinoma. In spite of having chronically elevated levels of vasopressin, these patients had normal blood pressures for their age and sex. Our results suggest that, although vasopressin is elevated in malignant hypertension, it does not contribute significantly to the raised blood pressure, and its increase is probably a consequence of volume shrinkage through renal salt and water loss.
J Cardiovasc Pharmacol 1986
PMID:Vasopressin and hypertension in man. 243 62

WRK1 cells, an established cell line derived from a chemically induced mammary tumor in the rat, are sensitive to vasopressin. Binding studies with intact WRK1 cells indicated the presence of a single population of [3H]vasopressin binding sites (dissociation constant, Kd = 12.7 +/- 0.2 nM, maximal binding capacity = 75 +/- 6 fmole/10(6) cells). Competition experiments using a series of vasopressin analogs with enhanced selectivity for the three subtypes of receptors already characterized--that is, renal V2 receptors, V1 receptors of the vascular or hepatic subtype (V1a), and V1 receptors from rat adenohypophysis (V1b)--indicated that vasopressin receptors from WRK1 cells have a ligand specificity very similar, if not identical, to that of V1a receptors. Vasopressin induced a marked (up to tenfold) increase in the production of labeled inositol phosphate (Ins 1,4,5 P3, Ins 1,4 P2, and Ins P) by WRK1 cells prelabeled with [3H]inositol. Antagonists of the vasopressor effect of vasopressin inhibited vasopressin-induced inositol lipid breakdown in WRK1 cells. For the entire series of vasopressin analogs tested, there was a close correlation between the respective Kd values for binding of these peptides to WRK1 cells and the corresponding Ka or Ki values derived from the determination of dose-dependent stimulation of inositol phosphate production, or inhibition of vasopressin-induced stimulation.
J Cardiovasc Pharmacol 1986
PMID:WRK1 cells: a model system for studying properties of V1a vasopressin receptors. 243 65

Cigarette smoking is a major risk for coronary atherosclerosis, but the mechanism of this is still unclear. The present study demonstrates that smoking produces a variable increase in plasma vasopressin concentration but that sensitivity of platelets to this elevated endogenous vasopressin release is blunted. This suggests that cigarette smoking contributes to atherosclerosis through the vascular effects of the hormones whose release it stimulates rather than by platelet activation. The mechanism for this blunted responsiveness to vasopressin was also investigated in vitro. The rise in intracellular free calcium concentration of platelets was markedly reduced following a second administration of vasopressin, whereas the in vitro shape change response was usually unaltered and could only be reduced with specific procedures for platelet preparation. This suggests that only a small increase of intracellular free calcium is necessary for a complete shape change response induced by vasopressin. The results indicate that the shape change is mediated by an increase in intracellular free calcium which is independent from the phosphoinositol pathway and the calcium is released from intracellular pools other than by those activated by serotonin or thrombin.
J Cardiovasc Pharmacol 1986
PMID:Smoking-induced increases in plasma vasopressin and reduced platelet hormone sensitivity. 243 66

The nonapeptide vasopressin is synthetized as part of a longer common precursor polypeptide, together with its carrier protein neurophysin and a glycopeptide of unknown function. The gene for this common precursor has been isolated and sequenced and shown to comprise three exons encoding, respectively, the protein domains approximately corresponding to the N-terminal leader peptide and hormone, to most of the neurophysin, and to the glycopeptide. In the Brattleboro rat, the hereditary hypothalamic diabetes insipidus, characteristic of this strain, has been shown to be caused by a single nucleotide deletion in the vasopressin gene. This leads to the much reduced synthesis of a mutant vasopressin precursor, whose C terminus is quite unlike that in wild-type rats and which does not appear to be correctly processed in vivo.
J Cardiovasc Pharmacol 1986
PMID:Biosynthesis of vasopressin. 243 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>