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)

The effect of cholesterol enrichment on vascular smooth muscle cell (VSMC) calcium homeostasis was studied by evaluating calcium uptake, efflux, and intracellular content in cultured VSMC derived from the rat pulmonary artery. Incubation of VSMC with liposomes consisting of free cholesterol (FC) and phospholipid (2:1 molar ratio, 1 mg FC/ml medium) for 24 h resulted in a 69 +/- 19% increase (P less than 0.01; n = 10) in FC which was associated with a 73 +/- 11% increase (P less than 0.005; n = 10) in intracellular calcium content as assessed by isotopic equilibrium with 45Ca2+ and a 65 +/- 11% increase (P less than 0.024; n = 3) as assessed by atomic absorption spectroscopy. Cholesterol enrichment caused a marked increase in the unidirectional calcium uptake rate from 0.026 +/- 0.03 to 0.158 +/- 0.022 nmol calcium/s per mg protein (P less than 0.01; n = 3), but had no effect on calcium efflux. Nifedipine (1 microM) reduced (P less than 0.05; n = 6) the effect of cholesterol enrichment on unidirectional calcium uptake by 78 +/- 16%; and verapamil (10 microM), diltiazem (1 microM), and nifedipine (1 microM) each significantly inhibited the effect of cholesterol enrichment on intracellular calcium accumulation. Exposure of cholesterol-enriched VSMC to cholesterol-poor liposomes for 24 h returned both FC and calcium contents to control levels. Serum- and serotonin-stimulated calcium uptakes were potentiated 3.7- and 1.7-fold, respectively, in cholesterol-enriched VSMC, whereas endothelin, vasopressin, and thrombin-stimulated calcium uptakes were not affected. We conclude that VSMC FC content plays a role in regulating cellular calcium homeostasis, both under basal conditions and in response to selected agonists.
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PMID:Cholesterol enrichment increases basal and agonist-stimulated calcium influx in rat vascular smooth muscle cells. 175 51

The effects of cilazaprilat were assessed on endothelium-dependent relaxations and contractions in isolated canine arteries. In coronary arteries incubated with indomethacin, cilazaprilat potentiated endothelium-dependent relaxations to bradykinin. In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin. To verify whether this effect was solely due to inhibition of the converting enzyme, the effects of cilazaprilat on responses to a variety of endothelium-dependent vasoactive agents were assessed. Endothelium-dependent relaxations to acetylcholine, thrombin, and vasopressin were not altered significantly by cilazaprilat. However, those induced by ADP and aggregating platelets were enhanced significantly by the compound. Endothelium-dependent relaxations to ADP-beta-S were augmented significantly but to a lesser extent. Furthermore, in the presence of the nitric oxide synthase antagonist NG-nitro-L-arginine, ADP-beta-S still caused small relaxations that were possibly mediated by endothelium-derived hyperpolarizing factor. These relaxations were augmented by cilazaprilat. Thus, the augmentation of purinergic relaxations may involve an increased production of endothelium-derived relaxing factors in addition to the protection of ADP from breakdown. Cilazaprilat did not affect endothelium-dependent contractions to acetylcholine or the calcium ionophore A23187 in canine basilar arteries, previously shown to be mediated by superoxide anions. Thus, cilazaprilat is not a scavenger of superoxide anion. Because this agent potentiates endothelium-dependent relaxations to bradykinin, ADP, and aggregating platelets, the present study suggests that, in addition to the lowering of plasmatic levels of angiotensin II, the antihypertensive and cardioprotective effects of cilazaprilat are mediated through an increased production of endothelium-derived relaxing factors.
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PMID:Effects of the converting enzyme inhibitor cilazaprilat on endothelium-dependent responses. 191 98

The efficacy and specificity of a novel synthetic thrombin inhibitor, DuP 714, on thrombin-induced elevation of cytoplasmic calcium, fibrinogen binding and aggregation in human platelets were examined. Thrombin (0.5 U/ml) stimulated an increase in [125I]fibrinogen binding in gel-filtered platelets which was blocked by DuP 714 with an IC50 value of 2 nM. Thrombin (1 U/ml)-induced elevation of intracellular [Ca2+]i was also blocked by DuP 714 with an IC50 value of 67 nM. A much higher concentration of thrombin (25 U/ml) was used to stimulate aggregation with heparinized platelet-rich plasma. Under these conditions, micromolar concentrations of DuP 714 were needed to inhibit thrombin. In all of these preparations, DuP 714 at concentrations as high as 10(-5) M had no intrinsic effects and did not affect the responses induced by arachidonate, ADP, collagen, epinephrine, vasopressin and serotonin. These data indicate that DuP 714 is a potent and specific thrombin inhibitor capable of arresting the actions of thrombin on human fibrin formation and platelet aggregation and secretion. It may serve as a potential antithrombotic agent for various forms of thrombotic disorders.
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PMID:Inhibition of the thrombin-platelet reactions by DuP 714. 193 Jan 90

To gain insight into the mechanisms that could account for the augmentation of cellular reactivity in primary hypertension, we have examined some of the biochemical events which are implicated in the transmission of mitogenic signal as well as in cell reactivity. This study focussed on phospholipase C, protein kinase C and GTP-binding proteins (G-proteins), in response to thrombin or arginin-vasopressin (AVP). Cultured fibroblasts prepared from the adventitia of thoracic aorta of spontaneously hypertensive rat (SHR) were used as cell models and were compared with fibroblasts prepared from controls Wistar-Kyoto (WKY) rats. The mitogenicity of each agonist was estimated by measuring the incorporation of 3H-thymidine into the newly synthesized DNA. The agonist-induced phospholipase C activity was evaluated by measuring the production of 3H-inositol phosphates in cells prelabeled with 3H-inositol. The influence of protein kinase C and that of G proteins on the mitogenesis in cells stimulated by thrombin or AVP was determined by pretreating cells with phorbol 12-myristate, 13-acetate (TPA) and pertussis toxin, respectively. Kinetics and dose response studies have demonstrated that in response to thrombin and AVP, the phospholipase C activity and the incorporation of 3H-thymidine were significantly higher in the fibroblasts derived from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activation mechanisms by thrombin and vasopressin of fibroblasts in spontaneously hypertensive rats]. 195 75

Sodium vanadate (11 microM) amplified the PGI2 production of rat liver cells (the C-9 cell line) incubated with thrombin, platelet activating factor, lysine-vasopressin, the Ca2(+)-ionophore A-23187, interleukin-1 beta, 12-tetradecanoylphorbol-13-acetate, teleocidin, epidermal growth factor, palytoxin, thapsigargin and colchicine but not that stimulated by exogenous arachidonic acid. Sodium vanadate (2.2 microM) also amplified PGF2 alpha production of dog kidney cells (the MDCK cell line) incubated with norepinephrine and, at 0.4 microM, PGI2 production of bovine aorta smooth muscle cells stimulated by serotonin. Sodium vanadate (55 microM) did not affect production of PGE2 and PGF2 alpha in rat basophil leukemia cells (the RBL-1 cell line) stimulated by the Ca2(+)-ionophore A-23187, but did inhibit synthesis of peptide-containing leukotrienes and 12-hydroxyeicosatetraenoic acid. When used with cultured cells at micromolar concentrations, vanadate is known to inhibit protein tyrosine-phosphate phosphatases. These results suggest that in some cells deesterification of lipids is positively regulated, at least in part, by phosphorylation of tyrosine whereas in leukocytes, lipoxygenase activities are negatively regulated, at least in part, by phosphorylation of tyrosine.
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PMID:Actions of vanadate on arachidonic acid metabolism by cells in culture. 202 Jul 48

Experiments were designed to study the effects of perindoprilat (S 9780) on endothelium-dependent and -independent relaxations and contractions in isolated blood vessels. Rings of either canine femoral, basilar or left anterior descending coronary arteries, pulmonary veins, or thoracic aortas from normotensive and hypertensive rats were suspended in organ chambers for isometric tension measurement. Perindoprilat did not evoke endothelium-dependent or -independent relaxations of femoral arteries, basilar arteries, coronary arteries, or rat aortas. The compound did not affect the endothelium-independent relaxations induced by isoproterenol and nitroglycerin in canine femoral arteries. However, when given to rings of canine basilar and coronary arteries, increasing concentrations of perindoprilat potentiated the endothelium-dependent relaxation to bradykinin. In addition, the drug potentiated the endothelium-dependent relaxations to acetylcholine and thrombin in preparations of canine left anterior descending coronary arteries. In contrast, perindoprilat did not cause changes in tension when given in the presence of either adenosine diphosphate, serotonin, or arginine-vasopressin. The compound did not modify the endothelium-dependent contractions evoked by the calcium ionophore A23187 and acetylcholine in canine basilar arteries. It also did not alter endothelium-dependent contractions to arachidonic acid or to hypoxia in canine pulmonary veins or to acetylcholine in the aorta of the spontaneously hypertensive rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of perindoprilat on endothelium-dependent relaxations and contractions in isolated blood vessels. 204 12

This work examines the roles of elevated cytosolic Ca2+ and stimulation of protein kinase C in agonist and non-agonist-mediated alkaline shift of the cytosolic pH set point for activation of Na+/H+ antiport in human platelets. Ca2(+)-depleted and control platelets were subjected to phorbol 12-myristate 13-acetate, thrombin, vasopressin, and ionomycin in 1 mM or Ca2+ free, nominally bicarbonate free media. To measure the cytosolic pH set point for Na+/H+ antiport activation, cells were acidified to different levels using the sodium propionate method. In some experiments protein kinase C was inhibited by staurosporine. Both protein kinase C stimulation and elevation of cytosolic Ca2+ can produce an alkaline shift in the pH set point for activation of Na+/H+ antiport in human platelets. However, the effect of Ca2+i on the pH set point predominates that of protein kinase C stimulation. Cytosolic Ca2+ is a prerequisite for agonist-evoked alkaline shift in the cytosolic pH set point for activation of Na+/H+ antiport. The cytosolic Ca2+ level is also essential for maintaining the basal cytosolic pH. These findings underscore the central role of cytosolic Ca2+ under basal and stimulated states in regulating cytosolic pH of human platelets.
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PMID:Agonist-evoked alkaline shift in the cytosolic pH set point for activation of Na+/H+ antiport in human platelets. The role of cytosolic Ca2+ and protein kinase C. 217 33

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

The regulation of receptor-operated calcium channels of human platelets by phospholipid-dependent, Ca2+- and diacylglycerol-activated protein kinase C was studied. In order to induce the activation of endogenous protein kinase C, a cell-penetrable structural diacylglycerol analog, 4 beta-phorbol 12 beta-myristate-13 alpha-acetate (FMA), was used. Using two independent approaches, i. e., the fluorescent probe for Ca2+, quin-2, and 45Ca2+ absorption technique, it was demonstrated that FMA (10(-10) - 10(-8) g/ml) blocks Ca2+ influx into the platelets induced by aggregation factors, e. g., ADP, vasopressin, platelet activating factor, thrombin and thromboxane A2 receptor agonist U46619. The half-maximum inhibition of the receptor-sensitive influx of Ca2+ was observed at (3-6) X 10(-10) g/ml of FMA. Under physiological conditions, protein kinase C is activated with an increase in Ca2+ concentration in the cytoplasm in the presence of diacylglycerol. Since the above-mentioned inducers besides Ca2+ influx stimulate diacylglycerol synthesis, it was assumed that the activation of protein kinase C triggers a negative feedback mechanism which blocks the receptor-operated calcium channels.
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PMID:[Blocking with phorbol ester, a protein kinase C activator, of receptor-dependent platelet calcium channels]. 241 59

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.
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PMID:Vasodilating agents and platelet function: intracellular free calcium concentration, cyclic nucleotides, and shape-change response. 243 9


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