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)

We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.
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PMID:Phospholipase C responses in cells from spontaneously hypertensive rats. 156 63

To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library. The predicted bovine preproendothelin-1 consists of 202 amino acid residues and has a high percentage of homology to human, porcine, and rat preproendothelin-1 (70%, 81%, and 77%, respectively). Big endothelin-1, an intermediate form, consists of 39 residues differing only at position Val28 from porcine (Ile28) and His27 from rat (Arg27). The predicted 21-residue mature endothelin-1 is identical to human, porcine, rat, canine, and mouse endothelin-1. Northern blot analysis with the cloned cDNA as a probe demonstrated that a single 2.3-kb preproendothelin-1 messenger RNA (mRNA) is expressed not only in endothelial cells, but also in various bovine tissues, including lung, brain, heart, intestine, kidney, ovary, and urinary bladder. Angiotensin II and arginine vasopressin immediately and dose-dependently induced expression of preproendothelin-1 mRNA, whose effects were abolished by specific receptor antagonists. These findings suggest that stimulation of endothelin-1 secretion from endothelial cells by both agonists may be principally due to induction of preproendothelin-1 mRNA.
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PMID:Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. 159 77

The irreversibility of the contractile action of endothelin-1 (Et) and of its binding to its receptors are usually believed to be linked in a direct manner. Rat aortic strips were exposed to 25 nM Et for short periods of time that were sufficient to irreversibly saturate membrane receptor sites and then washed of unbound Et. Under these conditions, fast and transient contractile responses were observed. They were unlike the slow and irreversible contractions observed in the continued presence of the peptide. They were as fast as KCl, angiotensin II and vasopressin contractions. It is concluded that the irreversibility of Et contractions and of its interaction with its receptors can be uncoupled. The data also suggests that recycling of endocytosed Et receptors contributes to the sustained contractile action of the peptide.
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PMID:The irreversibility of endothelin action is a property of a late intracellular signalling event. 165 49

By means of intracellular recordings we have studied the actions of the vasoactive peptides endothelin-1 and -3 (ET-1, ET-3) and arginine vasopressin (AVP) on the membrane potential of astrocytes in explant cultures of rat spinal cord and brainstem. Addition of ET-1, ET-3 or AVP to the bathing solution at concentrations of 10(-8)-10(-6) M depolarized the membrane of the majority of glial cells studied. The AVP antagonist d(CH2)5(1), Tyr(Me)2, Arg8-vasopressin reversibly blocked the depolarizations by AVP. Our electrophysiological findings together with autoradiographic binding studies strongly suggest the existence of ET and AVP receptors on astrocytes.
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PMID:Electrophysiological evidence for the existence of receptors for endothelin and vasopressin on cultured astrocytes of rat spinal cord and brainstem. 166 42

The potent vasoconstrictor endothelin leads to smooth muscle cell depolarization and increases in intracellular Ca2+. Although effects of endothelin on calcium channels have been described, it also has been speculated that endothelim may activate additional ion channels. The purpose of the present study was to identify an alternative ion current that could play a role in depolarizing cells in response to vasoconstrictors like endothelin and vasopressin. The effects of endothelin, vasopressin, sarafotoxin S6b, and phenylephrine were assessed using whole-cell patch-clamp recordings from primary dissociated rat aortic or mesenteric arterial smooth muscle cells cultured for 24-72 hours. From the usual resting potentials of these cells of -50 to -60 mV, endothelin (1-100 nM) induced a depolarization via an increase in membrane conductance. This depolarization was phasic, oscillating repeatedly from the resting potential to a relatively depolarized level and back to the resting potential. From a holding potential of -60 mV, endothelin-1, endothelin-3, vasopressin, or sarafotoxin S6b (but not phenylephrine) induced transient inward currents that also could be phasic. In external sodium, lithium, or cesium (but not Tris) and in internal potassium or cesium, these currents reversed near 0 mV. Although nifedipine-insensitive, the inward currents were absent in zero calcium, barium, or strontium, or in the presence of cobalt or nickel. These results represent the first report of a nonselective cation current in primary vascular smooth muscle cells that is calcium dependent and that could be responsible for the depolarizations induced from the resting potential by vasoconstrictors such as endothelin.
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PMID:Endothelin induces a nonselective cation current in vascular smooth muscle cells. 171 35

To analyze the action of endothelin-1 (ET-1) on intracellular Ca ion ([Ca2+]i) handling, we have measured the [Ca2+]i transients in a cultured vascular smooth muscle cell (VSMC) line, A7r5, using two-dimensional microfluorophotometry. In the presence of 1 mM extracellular Ca2+ ([Ca2+]e), ET-1 (100 nM) induced a transient increase in [Ca2+]i due to Ca2+ release from sarcoplasmic reticulum and a subsequent sustained [Ca2+]i increase, suggestive of the entry via the voltage-dependent Ca2+ channel. The transient phase was heterogenous in the VSMC population; only two-thirds of VSMCs showed the phase, whereas all cells showed the sustained phase. To elucidate the cause of heterogeneity, we measured the [Ca2+]i using VSMCs cultured under two extreme conditions. When the cell cycle was arrested at the quiescent phase in the defined serum-free medium, the transient phase was observed in most cells. In contrast, when cell growth was promoted by the above medium plus PDGF (50 ng/ml), the [Ca2+]i response was completely abolished, whereas both the voltage-dependent Ca2+ channel and vasopressin-operated Ca2+ mobilization mechanism were universally preserved, irrespective of the culture conditions. These results may imply that the ET-1-mediated Ca2+ release mechanism is closely influenced by cell growth and preferentially effective at the quiescent phase.
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PMID:Cell growth-dependent expression of endothelin-1 provocable Ca2+ channels in cloned vascular smooth muscle cells. 172 27

The effect of endothelin-1 (ET-1) on vasoconstrictor responses of the endothelium-denuded perfused rabbit ear artery to 5-hydroxytryptamine (5-HT), histamine, and vasopressin (VP) was studied. In low concentrations with no vasoconstrictor action (0.1 and 0.3 nM), and in a concentration that increased the perfusion pressure by 70 mm Hg (1 nM), ET-1 significantly enhanced responses to the agonists studied; this enhancement was apparently mediated by an increased influx of extracellular calcium through voltage-operated channels, as it was abolished by the calcium channel antagonist nicardipine (10 nM). In contrast, higher concentrations of ET-1 (3 and 10 nM) inhibited responses to VP and 5-HT and this inhibitory effect was accentuated in the presence of nicardipine. The possible mechanism by which ET-1 exerts this inhibitory effect on vasoconstrictor responses is discussed. Because ET-1 is released from endothelial cells that are immediately adjacent to vascular smooth muscle cells, these modulatory effects of ET-1 on responses to endogenously present vasoconstrictors may play a role in vascular function.
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PMID:Effect of endothelin-1 on responses of isolated blood vessels to vasoconstrictor agonists. 172 43

Responses of blood pressure to intravenous (i.v.) or intracerebroventricular (i.c.v.) endothelin-1 (ET-1) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were investigated. Conscious male SHRs and WKY rats were used for the experiments. ET-1 (300-1,000 ng/kg) was injected intravenously in the i.v. experiments, or 30 and 100 ng/kg of ET-1 were injected into the lateral ventricle in the i.c.v. experiments. The initial depressor response to i.v. ET-1 was greater in SHRs (n = 10) than in WKY rats (n = 10) at 1,000 ng/kg (-54 +/- 6 vs. -41 +/- 3 mm Hg, mean +/- SEM, p less than 0.05). The subsequent pressor response to i.v. ET-1 was smaller in SHRs than in WKY rats (3.5 +/- 0.8 vs. 7.0 +/- 0.9 mm Hg at 300 ng/kg, p less than 0.05, and 11 +/- 2 vs. 17 +/- 2 mm Hg at 1,000 ng/kg, p less than 0.05). Pressor responses to i.c.v. ET-1 were not different in SHRs (n = 8) and WKY rats (n = 8) at both doses (10 +/- 4 vs. 10 +/- 3 mm Hg at 30 ng/kg, and 46 +/- 10 vs. 49 +/- 10 mm Hg at 100 ng/kg). A greater initial depressor response and a smaller subsequent pressor response to i.v. ET-1 were observed in SHRs than in WKY rats. The attenuated pressor response to intravenously administered ET-1 may be unique since vasoconstrictor responses to other known vasoactive substances such as angiotensin, catecholamines, or vasopressin are reportedly augmented in SHRs. We did not find any difference in responsiveness to i.c.v. ET-1 between SHRs and WKY rats.
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PMID:Blood pressure responses to intravenous or intracerebroventricular endothelin-1 in spontaneously hypertensive rats. 172 61

1. In anaesthetized rats, an i.v. injection of endothelin-1 (0.25 nmol kg-1) evoked a rapidly appearing (maximal effect within 15 s) and short lasting (3 min) fall in blood pressure with tachyphylaxis occurring so that it was reduced by 50% by the last of 4 injections given 10 min apart. This property was also shared by endothelin-2, endothelin-3 and vasoactive intestinal contractor (VIC). 2. Cross tachyphylaxis between the isopeptides occurred. However, under the same experimental conditions the hypotensive effects of acetylcholine, adenosine, atrial natriuretic peptide (ANP) and substance P were reproducible and not modified in animals in which endothelin-1 no longer lowered blood pressure. Thus, the mechanism of the hypotensive action of endothelin peptides is different from that of acetylcholine, adenosine, ANP, and substance P. 3. In pithed rats, endothelin-1 (0.25 nmol kg-1) and its precursor human proendothelin (h-proendothelin) (0.5 nmol kg-1) induced pressor responses of a similar magnitude, which for h-proendothelin (up to 5.0 nmol kg-1) were not preceded by a hypotensive phase. The pressor effects of endothelin-1, like those of vasopressin, were reproducible upon repeated i.v. injections. 4. Rats given a 10 min infusion (0.1 nmol kg-1 min-1) of endothelin-1 showed no hypotensive response to an i.v. bolus injection of endothelin-1, whereas animals pretreated with an equipressor infusion of h-proendothelin did not develop tachyphylaxis to endothelin-1. 5. In pitched rats, endothelin-1, at a dose inducing the same maximal increase in blood pressure as h-proendothelin, was approximately 3 fold more potent as a mesenteric vasoconstrictor than h-proendothelin. These results suggest that if h-proendothelin is processed to endothelin-1, this transformation is not uniform throughout the vascular system. 6. The pressor response of h-proendothelin in pithed rats was dose-dependently inhibited by phosphoramidon (2.5-5.0mgkg '). However, this compound did not antagonize the effects of endothelin-1(0.25 nmol kg- ) or those of h-proendothelin (0.5 nmol kg- ) once developed. 7. Although some of these results may suggest that h-proendothelin does not undergo in vivo conversion to endothelin-1, the results obtained with phosphoramidon suggest that h-proendothelin is converted into endothelin-1. Therefore, the amount of endothelin-1 so produced can elicit pressor responses or regional vasoconstriction, but is insufficient to lower blood pressure and to inhibit endothelin-1-induced hypotension. 8. The mechanism of the tachyphylaxis does not appear to be depletion of endothelium-derived relaxing factor, since agents coupled to the latter endogenous vasorelaxant substance do not exhibit crosstachyphylaxis with endothelin-1. It is suggested that upon repeated or sustained exposure to endothelin-1, the endothelin-1 receptors mediating hypotension decrease in number and/or undergo conformational changes making them refractory to activation. Alternatively, the depletion of a blood-borne agent responsible for the hypotension could be involved.
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PMID:Cross tachyphylaxis to endothelin isopeptide-induced hypotension: a phenomenon not seen with proendothelin. 178 22

The localization and colocalization of endothelin-1, arginine-vasopressin and serotonin in the endothelial cells of rabbit aorta in primary culture were investigated by preembedding and postembedding immunocytochemistry. These three substances were localized in the same population of cells, where they appeared in high proportions (greater than 60%). These findings indicate: 1) that the cell population is heterogeneous, and 2) that these substances are colocalized in some of the cultured endothelial cells. Double labeling in single cells has demonstrated the simultaneous presence of 1) endothelin and vasopressin, 2) vasopressin and serotonin, and 3) endothelin and serotonin. The immunolabeling dominated in the cytoplasmic matrix.
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PMID:Colocalization of endothelin, vasopressin and serotonin in cultured endothelial cells of rabbit aorta. 180 Sep 49


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