UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modification of endothelin effects by the calcium antagonist isradipine was investigated by infusion of 1.0 nM/kg endothelin, a dose known to cause profound vasoconstriction, into eight anesthetized rabbits, followed by an infusion of 10 micrograms/kg isradipine or its vehicle into four rabbits each. In a second series of experiments, only isradipine (same dose) or its vehicle was infused into six rabbits each. Endothelin increased blood pressure and caused systemic vasoconstriction, marked bradycardia, and cardiodepression (measured with a strain guage), yet decreased central venous pressure. The regional vascular effects (measured with microspheres) encompassed widespread vasoconstriction (especially to the kidneys, adrenals, stomach, cecum, and heart), but also a tendency for vasodilatation (hepatic artery). Isradipine decreased blood pressure in endothelin-treated and normal animals. It increased cardiac output more in the endothelin group. The interaction between endothelin and isradipine in the peripheral circulation was generally additive. Isradipine blunts many, but not all, endothelin effects, thus resembling the antivasoconstrictor effects of calcium antagonists against a variety of vasoconstrictor agents such as angiotensin II (Ang II) or vasopressin. Similar to these, endothelin appears to cause vasoconstriction by several mechanisms, one of which apparently involves L-channel activation. A specific interaction of endothelin with the L-channel appears unlikely.
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PMID:Attenuation of endothelin-induced regional vasoconstriction by isradipine: a nonspecific antivasoconstrictor effect. 169 3

The purpose of the present study was to determine whether Ang II releases adenosine from the perfused rat lung. Rat lungs were perfused in situ with a physiological salt solution and were loaded with [3H]adenosine. The release of 3H from the perfused rat lung in response to intra-arterial injections of Ang II and other hormones was quantitated. Studies were conducted in both normal rats and in rats that had been nephrectomized before surgery to avoid exposure of the lungs to high levels of endogenous Ang II. Bolus doses of Ang II (10(-12)-10(-7) mol) increased the efflux of 3H from the lungs. Analysis of this effluent by thin-layer chromatography indicated that most of the Ang II-induced release of 3H was [3H]adenosine. The maximal response was usually obtained with 10(-9) mol, and higher doses (10(-8) and 10(-7) mol) mobilized less [3H]adenosine, which suggested tachyphylaxis. The effect of exogenous Ang II on [3H]adenosine release was greatly enhanced when activation of the endogenous renin-angiotensin system was prevented with prior nephrectomy. Infusion of the Ang II selective antagonist, (1-Sar-8-Ile)-Ang II, blocked Ang II-induced [3H]adenosine release. Neither norepinephrine, bradykinin, nor vasopressin consistently released adenosine. We conclude that (a) Ang II can induce the release of adenosine from the perfused rat lung, (b) this effect is receptor mediated, (c) this response is somewhat selective for Ang II, and (d) exposure to high levels of exogenous or endogenous Ang II causes tachyphylaxis so that Ang II-induced adenosine release is attenuated.
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PMID:Angiotensin II-induced [3H]adenosine release from in situ rat lung. 169 51

1. We have examined whether an increase of renal vascular resistance is generally accompanied by an inhibition of renin secretion. The effects of vasoconstriction produced by angiotensin II (Ang II), arginine-vasopressin (AVP), and potassium (KCl) depolarization on vascular resistance and on renin release from isolated rat kidneys perfused at constant pressure of 100 mmHg were investigated. 2. Histological examination performed on some representative kidneys revealed that the tubular lumina of all segments within the cortex were patent and the brush borders of the proximal tubules were well preserved. The renal vasculature and the juxtaglomerular region appeared to be morphologically intact. By immunocytochemistry, renin-positive cells were found exclusively in the wall of the afferent arterioles. 3. Basal flow rate through isolated kidneys was 14.5 +/- 2.0 ml min-1 (g kidney weight (gkw))-1 (mean +/- S.E.M., n = 10). Under control conditions renin secretory rates were in the range of 30-40 (ng Ang I h-1) min-1 gkw-1. 4. Ang II (100 pM) caused a decrease of renal flow rate to 42 +/- 2% of control which was accompanied by a reduction of renin secretion rates by a factor of 4. 5. AVP (10 pM to 1 nM) reduced renal perfusate flow in a dose-dependent fashion to a minimum of 25 +/- 3% of control. The vasoconstrictor effect of AVP was paralleled by a concentration-dependent increase of renin secretory rates reaching a factor of maximally 5 when AVP was used at a concentration of 1 nM. The stimulatory effect of AVP on renin release could be mimicked by [deamino-Cys1, D-Arg8]-vasopressin (dDAVP), a vasopressin analogue with prevalent V2 receptor agonistic properties. In the presence of dDAVP (100 nM, 1 microM) renal flow rate reversibly increased by 8 and 12% of control values, respectively. 6. Depolarizing concentrations of KCl (30 mM) decreased perfusate flow to 20 +/- 4% of control. The vasoconstrictor effect of KCl was paralleled by an increase of the arterio-venous difference of perfusate renin activity to such an extent that the rate of renin release remained unaltered. 7. Our findings suggest that there exists no general inverse relationship between renal arteriolar resistance and renin secretion. Our study, moreover, does not support a functional role of potential operated calcium channels in the control of renin secretion. Finally, we conclude that V2 receptors are present on juxtaglomerular epithelioid cell membranes and mediate the stimulatory effect of AVP on renin release from isolated rat kidneys.
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PMID:Differential response of renin secretion to vasoconstrictors in the isolated perfused rat kidney. 181 82

Angiotensin II (Ang II) belongs to the family of the calcium-mobilizing hormones which includes other vasoactive hormones such as vasopressin, endothelin, serotonin. Angiotensin can be considered as an archetype for ligands activating the calcium messenger system. Observation of the changes occurring in the two branches of the calcium messenger system--the inositol 1, 4, 5-trisphosphate/calcium branch and the diacylglycerol/protein kinase branch--upon activation by Ang II in various target cells (adrenal zona glomerulosa cells, vascular smooth muscle cells and cardiomyocytes) emphasized common features but also revealed variation in the responses and in the interaction between the two branches (so-called cross-talk). For example, the use of single cell microfluorometry with fura-2 shows that, in adrenal glomerulosa cells, Ang II induces sinusoidal oscillations of cytosolic free calcium concentration which are typical of excitable cells; by contrast in vascular smooth muscle cells, one observes transient oscillations indicative of a mechanism of calcium-induced calcium release. Furthermore, the activation of protein kinase C by angiotensin II leads to negative feed-back mechanisms on the final biological response in adrenal cells and cardiomyocytes, whereas it has a potentiating effect in vascular smooth muscle cells. On-line video microscopy allows one to follow in real time the changes in cytosolic free calcium concentration in vascular smooth muscle cells and spontaneous beating cultured cardiomyocytes thereby revealing the spatial origin of the calcium "tide" spreading throughout the cytosol. The task is now to superimpose these calcium signals, these biochemical triggers and the framework of the cytoskeleton and intracellular organelles forming the stage of this play.
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PMID:[Transmembrane signal. Respective role of free cytosol calcium and of protein kinase C]. 182 87

To assess the mechanisms how angiotensin II (Ang II) given intracerebroventricularly (i.c.v.) induces natriuresis, the effects of Ang II (10 ng/kg/min, for 30 min) on the renin-angiotensin-aldosterone system, the release of vasopressin (AVP) and atrial natriuretic peptide (ANP) and on cardiovascular and renal functions were investigated in anesthetized dogs. In control dogs, vehicle alone (artificial cerebrospinal fluid) was infused at a rate of 10 microliters/min. Ang II given i.c.v. produced a gradual increase in urine flow, urinary sodium and potassium excretion and osmolar clearance, but had no effect on plasma ANP, aldosterone, arterial blood pressure, and renal blood flow. However, i.c.v. Ang II increased plasma AVP and decreased heart rate, plasma renin activity, inulin clearance and filtration fraction. In the cotrol group, vehicle treatment had no effect on these parameters except for decreases in inulin clearance and filtration fraction. These results suggest that circulating ANP and blood pressure may not play an important role in i.c.v. Ang II-induced natriuresis, but increased AVP release and decreased renal sympathetic nervous activity may contribute to the natriuresis.
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PMID:Responses of atrial natriuretic peptide, vasopressin, aldosterone and renal function to intracerebroventricular infusion of angiotensin II in dogs. 182 54

The homozygous Brattleboro rat (di/di) synthesizes a vasopressin (VP) precursor with a different C-terminus, which is not packaged in granules. In addition, the expression of a coexisting peptide, angiotensin II (Ang II), is disturbed. During postnatal life a small but increasing number of solitary post-mitotic hypothalamic neurons of the di/di rat undergoes a switch to a genuine heterozygous phenotype. Here we report the reappearance of Ang II in these heterozygous cells, which suggests that for the expression of Ang II a normal VP precursor is required. Based upon the present study and literature data it is proposed that at the level of the endoplasmic reticulum a compartmentalization of the synthesis of various peptide precursor occurs.
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PMID:Vasopressin and angiotensin II are absent but spontaneously reappear in solitary hypothalamic neurons of the homozygous Brattleboro rat. 188 32

Angiotensin II (Ang II) binding sites were characterized in primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. Binding of [3H]Ang II to BMECs was time dependent and saturable. Scatchard plot analysis of dose-dependent [3H]Ang II binding revealed a single population of binding sites (Kd = 3.1 nM, Bmax = 52 fmoles/mg protein). Sarathrin, an Ang II antagonist, and saralsin, a partial agonist, inhibited [3H]Ang II binding to BMEC monolayers, whereas two unrelated peptides, bradykinin and arginine-vasopressin, had no effect on the specific binding of [3H]Ang II. At 37 degrees C, [3H]Ang II was internalized in BMECs and this uptake appeared to be saturable. Nanomolar concentrations of Ang II and saralasin stimulated [3H]thymidine uptake in serum-free starved BMEC monolayers, corresponding to an increase in DNA synthesis. On the other hand, sarathrin had no effect on [3H]thymidine uptake. The affinity of the single population of Ang II of binding sites was consistent with the concentration range of Ang II actions demonstrated in several cell types including BMECs. The Ang II-mediated actions on DNA synthesis suggest that this peptide-hormone may possess growth regulating properties in BMECs through either surface or internal site interactions. Collective findings support the complex nature of Ang II in regulating vascular and nonvascular cell growth and permeability characteristics.
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PMID:Some characteristics of specific angiotensin II binding sites on bovine brain microvessel endothelial cell monolayers. 192 32

Some simple N-benzylimidazoles, originally described by Takeda Chemical Industries (Osaka, Japan), were characterized to be very weak but selective nonpeptide angiotensin II (Ang II) receptor antagonists with a competitive mode of action. Chemical modifications of these led to EXP6155 and EXP6803, which showed approximately 10- and 100-fold higher affinity, respectively, but were orally ineffective. Oral activity was obtained for the biphenyl carboxylic acid derivatives EXP7711 and especially EXP9654. A further advance in the design of nonpeptide Ang II receptor antagonists was provided by DuP 753, an analogue of EXP7711 in which the carboxylic acid function is replaced by its tetrazol-5-yl equivalent. DuP 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bi phe nyl-4- yl)methyl]imidazole, potassium salt) displaces radiolabeled Ang II from its specific binding sites in various tissues, affording IC50 values of approximately 20 nM. DuP 753 competitively antagonizes Ang II-induced responses in various in vitro and in vivo preparations but does not influence those to KCl, norepinephrine, vasopressin, and others, nor does it affect converting enzyme and renin. In high renin animal models of elevated arterial blood pressure, intravenous and oral administrations of DuP 753 produce a sustained decrease in pressure without influencing heart rate. Marked antihypertensive effects are observed in spontaneously hypertensive rats, but no efficacy is noticed in deoxycorticosterone acetate hypertensive animals. DuP 753 showed no agonistic properties in any of the above test systems and has been chosen to undergo clinical trials for the treatment of hypertension. In rats, the 5-carboxylic acid (EXP3174) represents a major metabolite of DuP 753.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II receptor antagonists. From discovery to antihypertensive drugs. 193 77

Endothelin (ET), a peptide originally isolated from the supernatants of cultured endothelial cells, exerts a wide variety of biological effects in different tissues. Endothelial-cell-synthesized ET-1 has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMC) in vivo, with effects that include both vascular reactivity (vasodilation/vasoconstriction) and mitogenesis. This study, by the use of immunocytochemically characterized SMC (rVSMC) isolated from the aortas of spontaneously hypertensive rats, has investigated a possible autocrine role for ET in regulation of the vasculature. Although quiescent cultures of rVSMC apparently did not constitutively express prepro ET-1mRNA, ET-specific transcripts could be induced by a variety of growth factors (transforming growth factor beta [TGF-beta]; platelet-derived growth factor-AA homodimer [PDGF-A chain]) and vasoactive hormones (angiotensin II [Ang II], arginine-vasopressin, and ET-1 itself). The kinetics for prepro ET-1mRNA induction in rVSMC were characteristically rapid in onset and transient. Down-regulation of protein kinase C by 48 h pretreatment of rVSMC with phorbol ester markedly reduced the subsequent ability of rVSMC to express ET-1 transcripts and secrete ET-1 peptide in response to Ang II. Inducible prepro ET-1mRNA expression was accompanied by a cycloheximide-inhibitable release of ET-1 peptide into the medium of rVSMC. ET-1 peptide was determined by both radioreceptor- and radioimmunoassay. Stimulated rVSMC accumulated ET-1 (approximately 200 pg.10(6) cells-1 x 4 h-1) at levels that attained biological relevance (approximately 10(-10) M). Sep-pak C18 extracts of medium from stimulated rVSMC elicited contraction of isolated endothelium-denuded rat mesenteric resistance vessels, and this response was characteristically protracted and difficult to "wash out." Synthetic (porcine) ET-1 promoted the expression of transcripts for PDGF-A chain, TGF-beta, and thrombospondin in quiescent rVSMC. Such effects of ET-1 on gene expression may be relevant to the mitogenic potential of ET-1 on VSMC. Our findings imply a role for ET-1 in the control of vascular function via both paracrine and autocrine regulatory mechanisms. The expression of prepro ET-1mRNA and peptide biosynthesis by rVSMC may have both short-term (e.g., vasoconstriction) and long-term (e.g., structural remodeling) consequences. A sustained loop of autocrine stimulation by ET-1 in SMC could contribute toward the pathogenesis of vasospasm and/or atherosclerosis.
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PMID:Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function. 207 71

1. The interaction between atrial natriuretic factor (ANF) and angiotensin II (Ang II) within the brain to influence renal function and blood pressure was studied in Inactin-anaesthetized male Sprague-Dawley rats. 2. Central infusion of ANF produced a diuresis which was associated with a significant decrease in plasma arginine vasopressin (AVP) level. There was no change in sodium excretion rate over the 80 min of intracerebroventricular ANF infusion and ANF produced no detectable change in mean arterial blood pressure. 3. Central Ang II administration produced a significant decrease in urine flow, which was associated with elevated plasma AVP, an increase in sodium excretion and a rise in mean arterial blood pressure. 4. Combined ANF and Ang II infusion produced an antidiuresis, which was associated with increased plasma AVP concentration. Both the natriuretic and vasopressor actions of central Ang II were abolished when ANF was co-administered. 5. It is concluded that ANF and Ang II interact centrally; ANF antagonizes the pressor and natriuretic effects but not the antidiuretic effects of central Ang II. These data suggest the possibility of distinct and separate sites within the brain through which Ang II influences vasopressin release and renal sodium handling and elevates blood pressure.
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PMID:The renal and vascular effects of central angiotensin II and atrial natriuretic factor in the anaesthetized rat. 214 82

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