UNIPROT:P01185 - FACTA Search

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)

Cultured glomerular mesangial cells are shown to produce a potent vasoconstrictive peptide, endothelin-1 (ET-1). We examined whether basal or stimulated ET-1 production by angiotensin II (Ang II) and arginine vasopressin (AVP) is enhanced in cultured mesangial cells of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). In addition, we examined which receptor subtypes of Ang II and AVP mediate ET-1 production in these cells. Basal ET-1 production in SHR mesangial cells was not different from that in WKY cells, although a trend toward increased ET-1 production was observed in the SHR cells. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner in mesangial cells of both rat strains, but Ang II- and AVP-induced stimulation of ET-1 production was clearly greater in SHR than WKY cells. The protein kinase C (PKC)-activating phorbol ester phorbol myristate acetate stimulated ET-1 production in a concentration-dependent manner in cells of both rat strains, but this stimulation was significantly greater in SHR than WKY cells. Neither Ang II nor AVP stimulated ET-1 production in PKC-depleted cells of both strains. Ang II- and AVP-induced stimulation was completely abolished by selective angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptor antagonists, respectively, in cells of both rat strains. These results suggest that AT1 and V1-receptor-mediated mesangial cell production of ET-1 is clearly enhanced in SHR compared with WKYs. Increased response of ET-1 production to PKC activation appears to contribute in part to the observed enhancement of ET-1 production in SHR mesangial cells.
...
PMID:Endothelin production in cultured mesangial cells of spontaneously hypertensive rats. 776 63

Several components are responsible for circulatory control at the central, regional, and microcirculatory level. Angiotensin-converting enzyme (ACE) inhibitors are known to act beneficially on circulation by various mechanisms. The influence of continuous i.v. administration of the ACE inhibitor enalaprilat on regulators of circulation was studied in 45 critically ill patients. According to a prospective randomized sequence, either 0.25 mg/h (group 1, n = 15) or 0.5 mg/h (group 2, n = 15) of enalaprilat or saline solution as placebo (control group, n = 15) were continuously given. Infusion was started on the day of admission to the intensive care unit (ICU) and continued for the next 5 days. From arterial blood samples, plasma levels of endothelin-1 (ET), atrial natriuretic peptide (ANP), renin, vasopressin, angiotensin-II, and catecholamines (epinephrine, norepinephrine) were measured. All measurements were carried out before infusion (= baseline values) and during the next 5 days. In both enalaprilat groups, mean arterial blood pressure (MAP) decreased similarly; heart rate (HR) and central venous pressure (CVP) did not change, and were without differences in comparison to the untreated control. Except for ET, plasma levels of all vasoactive substances exceeded normal range at baseline. Angiotensin-II plasma concentrations significantly decreased during enalaprilat infusion (0.25 mg/h: from 53.1 +/- 11.3 to 22.1 +/- 9.3 pg/ml; 0.50 mg/h: 62.1 +/- 14.4 to 17.9 +/- 7.9 pg/ml), but they remained significantly elevated in the untreated control patients. Vasopressin plasma level increased only in the control group (p < 0.01) and decreased in the patients in whom 0.50 mg/h of enalaprilat was infused.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Continuous i.v. administration of the angiotensin-converting enzyme inhibitor enalaprilat in the critically ill: effects on regulators of circulatory homeostasis. 776 7

1. In vivo the effects of endothelin-1 (ET-1) are limited by its rapid removal from the circulation and possibly by its metabolism by enzymes such as neutral endopeptidase 24.11, deamidase or carboxypeptidase A. Here, using as a model the isolated perfused mesenteric arterial bed of the rat, we have examined the involvements of these enzymatic activities in the vascular responses to ET-1. 2. Samples of Krebs buffer which had been recirculated through the mesenteric arterial bed for 30 min rapidly destroyed the activity of ET-1 as assessed either by bioassay on rings of rat thoracic aorta or by high performance liquid chromatography (h.p.l.c.). For instance, after 15 min incubation with the recirculated-Krebs solution (recirc-K) the contraction induced by 3 x 10(-9) M ET-1 was reduced by more than 90%. Contractions induced by sarafotoxin 6b (3 x 10(-9) M) were similarly suppressed by preincubation with recirc-K whereas those to Arg-vasopressin (3 x 10(-9) M) were unaffected. 3. The degradation of ET-1 by recirc-K was prevented by 1,10-phenanthroline (10(-3) M), abolished by heating the recirc-K solution to 90 degrees C for 15 min, and reduced by EGTA (5 x 10(-3) M) or ET-1(16-21) (10(-5) M). For instance, in the presence of ET-1(16-21) (n = 6) the contraction induced by ET-1 was reduced by only 40% after 15 min incubation with recirc-K buffer. Leupeptin (3 x 10-4 M), dichloroisocoumarin(5 x 10-5 M), phenylmethyl-sulphonyl fluoride (10-3 M), a combination of bacitracin (300 mg ml-1),bestatin (10-5 M), captopril (10-5 M), phosphoramidon (10-4 M) and thiorphan (10-4 M) or Polypep (aproprietary protein digest) did not inhibit the degradation of ET-1 by recirc-K.4. In experiments examining directly the vascular responses of the isolated perfused mesentery of the rat, the addition of cumulative concentrations of ET-1 to the recirculating Krebs solution caused small concentration-dependent increases in perfusion pressure. The inclusion of ET-1(16-2l), ET-1(17-21), or ET-1(18-21) (10-5M) greatly potentiated these responses, but not those to Arg-vasopressin or methoxamine.The effects of 1,10-phenanthroline or EGTA could not be examined in this system because these agents both depressed non-specifically the vasoconstrictor responses of the mesenteric vascular bed.5. Thus, the rat mesentery releases an enzyme that very rapidly destroys ET-1 or the very closely related peptide, sarafotoxin 6b but not Arg-vasopressin. This enzyme is most probably a metallopeptidase because of its sensitivity to inhibition by 1,10-phenanthroline or EGTA. It is particularly interesting that a simple vascular bed such as the mesentery produces such a powerful endothelin metabolising enzyme. It is tempting, therefore, to speculate that the endothelin degrading enzyme active at neutral pH that- we have found is important in the metabolism of ET-1 throughout the vasculature.
...
PMID:Rapid degradation of endothelin-1 by an enzyme released by the rat isolated perfused mesentery. 777 48

Increased peripheral resistance is the hallmark of hypertension. It may result in part from exaggerated vascular reactivity of resistance arteries. Some changes in density of surface receptors for different vasoconstrictors and vasorelaxants have been described that could play a role in physiological findings in hypertension. Smooth muscle cells of resistance arteries have increased cytosolic free calcium concentration in some models of experimental hypertension, which may contribute to enhance vascular responses. Exaggerated response of the inositol phosphate-calcium pathway has been demonstrated after stimulation with some vasoconstrictor agents such as norepinephrine, angiotension II, and vasopressin. In contrast, responses to the potent vasoconstrictor peptide endothelin-1 are either normal (in spontaneously hypertensive rats) or blunted (in deoxycorticosterone-salt hypertension). In the latter case, endothelin receptor density, inositol phosphate and diacylglycerol generation, and cytosolic calcium responses agree with blunted response of blood vessels. Increased basal cytosolic calcium and exaggerated sensitivity of myosin light chain to calcium may be mechanisms underlying increases in sensitivity of signal transduction in smooth muscle in some models of hypertension. However, in general, signal transduction of receptors for vasoconstrictors appears to be blunted rather than exaggerated, except for responses to angiotensin II. Altered structure of resistance arteries (remodeling) may be a mechanism that, even in presence of blunted intracellular signal transduction, may result in enhanced pressor responsiveness of blood vessels in hypertension.
...
PMID:Intracellular signal transduction for vasoactive peptides in hypertension. 783 83

Endothelin is a 21-amino-acid, vasoactive peptide. Sequence analysis of cloned cDNAs for porcine and human endothelin precursors showed that endothelin-1 (ET-1) is produced in the endothelial cells. The peptide, endothelin (ET), was first identified as a potent vasoconstrictor. It is one of the most potent endogenous vascular smooth-muscle constrictors, ten times more potent than angiotensin II, vasopressin, and neuropeptide Y. Shortly after the discovery of this vasoconstrictor peptide, it was revealed that endothelin also possesses vasodilator properties at doses lower than those necessary to produce vasoconstriction. However, controversy still exists over the mechanism(s) of action; prostacyclin and endothelium-derived relaxing factor (EDRF) have mainly been implicated as the source of the initial vasodepressor effect. ET also elicits markedly different regional hemodynamic response patterns. There is a heterogeneity in the observed vasodilation or vasoconstriction, depending on species and on vascular beds studied in the same species. Endothelin has been implicated in a number of pathologic situations, including tissue ischemia and vasospasm. ET seems to be produced more actively around the site of endothelial damage; the loss of balance between its vasodilator- and vasoconstrictor-induced responses could contribute to its patho-physiologic properties. Experimental results strongly support the concept that ET could be important in controlling vascular tonus, both in the healthy and the diseased vessel.
...
PMID:Endothelin: an endothelium-derived vasoactive peptide. 788 38

This study evaluated the assessment of plasma endothelin-1 (ET-1) levels in primary aldosteronism and its correlation with other vasoactive hormones such as renin, aldosterone, catecholamines, arginine-vasopressin, and atrial natriuretic peptide. Plasma ET-1 was measured in 12 patients with primary aldosteronism (five adenomas and seven primary hyperplasia) and in 15 normal subjects. No significant differences were found in plasma ET-1 between controls and hypertensive patients both in adenoma and primary adrenal hyperplasia (8.8 + 1.6 pg/mL v 6.2 + 1.4 pg/mL v 6.5 + 1.0 pg/mL, P = NS, respectively). Further, no significant correlations were found among ET-1 and vasoactive hormones. In conclusion, these findings show that there are no differences in ET-1 levels between primary aldosteronism patients and healthy subjects. Circulating ET-1 is not involved in the hypertension in primary aldosteronism.
...
PMID:Plasma immunoreactive endothelin-1 in primary hyperaldosteronism. 791 56

The effectiveness of intradermal (i.d.) BQ-123 (cyclo[D-Asp-Pro-D-Val-Leu-D-Trp]) and i.d. Ro 47-0203 (bosentan, 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyr imidin-4 - yl]-benzene-sulfonamide) has been evaluated on local microvascular responses to endothelin-1 and endothelin-3, measured by a multiple site 133Xe clearance technique in rat skin in vivo. Intradermal injection of endothelin-1 (0.3 pmol/site) and endothelin-3 (10 pmol/site) induced a similar (approximately 50-60%) decrease in basal blood flow in rat skin. BQ-123 (3-1000 pmol/site), a selective endothelin ETA receptor antagonist, caused a significant dose-dependent decrease in the vasoconstriction induced by endothelin-1 (P < 0.05) but was less effective on vasoconstriction induced by endothelin-3. Bosentan (3-1000 pmol/site), a new non-peptide mixed antagonist of endothelin ETA and endothelin ETB receptors, significantly reduced the vasoconstriction induced by endothelin-1 but was less effective than BQ-123. BQ-123 and bosentan were similarly effective as antagonists of endothelin-3. BQ-123 and bosentan had no effect on basal blood flow and no inhibitory activity on vasoconstriction induced by vasopressin (0.03 pmol/site) or phenylephrine (300 pmol/site). These findings indicate that BQ-123 and bosentan are effective and selective inhibitors of the vasoconstriction induced by endothelins in the rat skin microvasculature.
...
PMID:Effect of BQ-123 and Ro 47-0203 (bosentan) on endothelin-induced vasoconstriction in the rat skin. 795 19

The effect of short-term nicotine consumption on endothelin-1 (ET-1) levels was studied in 10 male healthy smokers. Volunteers smoked in random order on 3 separate days a low-tar cigarette or a high-tar cigarette, or were studied without having smoked (no-cigarette experiment). ET-1, corticotropin, and cortisol levels, heart rate, and blood pressure were determined before and 1, 3, 5, 10, 20, and 30 minutes after smoking. In contrast to results obtained after smoking a low-tar cigarette or not smoking, smoking a high-tar cigarette resulted in a significant increase in ET-1 levels within 10 minutes, followed by an increase in corticotropin levels within 20 minutes after smoking. Thirty minutes after smoking, cortisol levels were higher after a high-tar cigarette compared with a low-tar cigarette or no smoking. Increases in heart rate and systolic blood pressure were likewise higher after smoking a high-tar cigarette than after smoking a low-tar cigarette. In conclusion, it is tempting to speculate that ET-1 may indeed act as the long-searched-for link between vasopressin and corticotropin-releasing hormone (CRH) and thus play an essential role in the stimulation of the hypothalamic-pituitary-adrenal axis. In addition, these results suggest that the increase in the level of ET-1, a powerful vasoconstrictor and mitogen, may play an important part in the disease mechanisms of atherosclerosis arising from smoking.
...
PMID:Elevated endothelin-1 levels after cigarette smoking. 813 72

We examined the role of endogenous opioids in cardiovascular and neurohormonal responses to intracerebroventricular (icv) endothelin-1 (ET-1) in conscious rabbits. With or without pretreatment with intravenous naloxone (1 mg/kg), the effects of icv ET-1 (25 pmol/kg) on cardiovascular and neurohormonal responses were examined. ET-1 (icv) caused significant increases in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), plasma catecholamines, and vasopressin levels. Naloxone pretreatment significantly augmented the increases in MAP and RSNA induced by icv ET-1. To clarify the mechanism of these effects, we also examined the effects of naloxone and naloxone methobromide, which does not cross the blood-brain barrier, on baroreceptor reflex. Intravenous naloxone (1 mg/kg) attenuated the baroreflex sensitivity assessed by RSNA (Smax: -9.9 +/- 1.7 vs. -6.9 +/- 1.2, P < 0.01); however, intravenous naloxone methobromide failed to alter the baroreflex sensitivity. Furthermore, in sinoaortic-denervated rabbits, naloxone pretreatment did not affect the increase in MAP induced by (icv) ET-1. These results suggest that intravenous naloxone acts in the central nervous system to attenuate the baroreflex sensitivity, which might augment the increases in MAP and RSNA induced by icv ET-1 in conscious rabbits.
...
PMID:Naloxone augments sympathetic outflow induced by centrally administered endothelin in conscious rabbits. 818 85

Addition of endothelin-1 or endothelin-3 to rat renal papillary tubules produced a dose-dependent inhibition of the cAMP response to vasopressin stimulation. The average EC50 values were 1.1 +/- 0.6 and 2.6 +/- 1.1 nM, respectively, indicating mediation by an endothelin ETB receptor. Phorbol myristate acetate (1 microM) also inhibited the vasopressin-cAMP response and this inhibition was not additive with that to endothelin, indicating that the endothelin inhibition is mediated by activation of protein kinase C. These findings demonstrate functionally relevant endothelin ETB receptors on renal papillary tubules. Such receptors are a possible target for endothelin-3 produced within the kidney.
...
PMID:Functional endothelin ETB receptors on renal papillary tubules. 825 66

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