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)

Angiotensin II (AII)- and Arg8-vasopressin (AVP)-regulated gene expression in vascular cells has been reported to contribute to vascular homeostasis and hypertrophy. In this report, AVP-induced expression of plasminogen activator inhibitor (PAI)-2 mRNA in rat microvessel endothelial (RME) cells was identified using differential mRNA display. Further characterization of vasoactive peptide effects on PAI expression revealed that AII stimulated a 44.8 +/- 25.2-fold and a 12.4 +/- 3.2-fold increase in PAI-2 mRNA in RME cells and rat aortic smooth muscle cells (RASMC), respectively. AII also stimulated a 10- and 48-fold increase in PAI-1 mRNA in RME cells and RASMC, respectively. These AII effects were inhibited by either Sar1, Ile8-angiotensin or the AT1 antagonist DuP 735, but were not significantly altered in the presence of the AT2 antagonist PD123319. AII stimulation of RASMC and RME cells also significantly increased both PAI-1 protein and PAI activity released to the culture medium. Inhibition of protein kinase C completely blocked PMA-stimulated induction of PAI-2 mRNA in both cell types and inhibited the AII-stimulated increase in RASMC by 98.6 +/- 2.8%. In contrast, protein kinase C inhibition only partially decreased the AII-stimulated PAI-2 expression in RME cells by 68.8 +/- 11.1%, suggesting that a protein kinase C-independent mechanism contributes to a 6.9 +/- 1.5-fold AII induction of PAI-2 expression in endothelial cells. AII and PMA also stimulated protein tyrosine phosphorylation in RME cells, and the tyrosine kinase inhibitor genistein partially blocked their induction of PAI-2 mRNA. These findings suggest that AII may regulate plasminogen activation in the vasculature by inducing both PAI-1 and PAI-2 expression.
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PMID:Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. 788 82

1. The effect of GR117289, an angiotensin AT1 receptor antagonist, on diastolic blood pressure (DBP) was determined in angiotensin-dependent and angiotensin-independent models of hypertension in rats. In addition, the antagonist profile of GR117289 at angiotensin AT1 receptors was determined in conscious renal hypertensive rats and conscious normotensive rats, dogs and marmosets. 2. Intra-arterial and oral administration of GR117289 (0.3-3 mg kg-1, i.a.; 1-10 mg kg-1, p.o.) to 6-day left renal artery ligated hypertensive (RALH) rats (DBP > 140 mmHg) produced significant, dose-related reductions in DBP with little apparent effect on heart rate (< 15%). The antihypertensive effect of GR117289 developed progressively over several hours and with some doses persisted for 24-48 h after administration. 3. Administration of GR117289 (1 mg kg-1, i.a.) on 5 consecutive days to RALH rats reduced DBP on each day. The antihypertensive effect of GR117289 was not cumulative as DBP had almost returned to base-line values, 24 h after administration of each dose. 4. A dose of GR117289 (3 mg kg-1, i.a.), which produced a substantial reduction in DBP (about 70 mmHg) in RALH rats, was administered to rats in which blood pressure was elevated either by unilateral renal artery clipping, sustained infusion of angiotensin II (AII), DOCA-salt administration or genetic inbreeding. GR117289 reduced DBP in rats in which the renin-angiotensin system was activated by renal artery clipping or AII infusion but had little effect in normotensive rats, DOCA-salt rats and SHR. 5. Systemic administration of All to RALH rats and to normotensive rats, dogs and marmosets elicited reproducible pressor responses in all species. Systemic or oral administration of GR1 17289 (3 mg kg-1)inhibited the pressor responses produced by All, resulting in parallel, rightward displacements of All dose-response curves.6. Maximal displacements of All dose-response curves occurred 1 h and 1-7 h after systemic and oral administration, respectively. GR1 17289 produced a 32-246 fold displacement after systemic administration and a 4-12 fold displacement after oral administration. The effect in dogs was short lasting after systemic administration but the effect of GRI17289 lasted for up to 24 h in rats and marmosets and for up to 24 h after oral administration in all species. The antagonist activity appeared specific for angiotensin receptors as GRi17289 did not inhibit pressor responses to phenylephrine or vasopressin.7. These experiments demonstrate that GRI 17289 reduces blood pressure in conscious hypertensive rats after both systemic and oral administration, and is an effective antagonist at angiotensin AT1 receptors in conscious rats, dogs and marmosets.
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PMID:Cardiovascular effects of GR117289, a novel angiotensin AT1 receptor antagonist. 801 89

1. In this article we review the physiological actions of the heptapeptide angiotensin-(1-7) [Ang-(1-7)] at the periphery and on central pathways involved in the control of arterial pressure. Peripherally Ang-(1-7) has been shown to present a potent antidiuretic effect on water-loaded rats. Microinjection of pmol amounts of Ang-(1-7) into the dorsomedial or ventrolateral medulla (VLM) of anesthetized rats produces cardiovascular effects comparable to Ang II. In addition, in vitro experiments have shown that Ang-(1-7) has a potent vasopressin and prostaglandin releasing activity and excites neuronal activity in the hypothalamus and medulla. 2. Evidence for the existence of a new angiotensin receptor subtype that mediates the central cardiovascular actions of this active peptide of the renin-angiotensin system (RAS) is also provided. Neither the AT1 receptor antagonist DUP 753 or the AT2 receptor antagonist CGP 42112A blocked the pressor response produced by microinjection of Ang-(1-7) into the rostral VLM. However, the effect of Ang-(1-7) on VLM was completely abolished by the non-specific angiotensin receptor antagonist, Sar1-Thr8-Ang II. 3. The data presented here reinforce the hypothesis of the existence of complex site-specific interactions between multiple angiotensins and multiple receptors in the mediation of important central and peripheral effects of the RAS.
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PMID:Central and peripheral actions of angiotensin-(1-7). 808 84

The cardiovascular effects of angiotensin II were examined in aortic blood pressure-controlled and -uncontrolled pithed rats. Angiotensin II induced a dose-dependent increase in diastolic blood pressure, left ventricular pressure (LVP), dP/dt (the first derivative of LVP) and heart rate in pithed rats. The maximal responses for these parameters were similar to those to noradrenaline, except for the rise in diastolic blood pressure, where noradrenaline caused a greater increase than angiotensin II. After treatment with propranolol, the positive chronotropic effect of angiotensin II was abolished. Angiotensin II produced a dose-dependent increase in diastolic blood pressure, which was similar to that of vasopressin, and an increase in dP/dtmax, which proved much greater than that of vasopressin. When aortic blood pressure was controlled and the beta-receptors were blocked by propranolol, angiotensin II caused a dose-dependent increase in dP/dtmax without affecting the left ventricular enddiastolic pressure. The same results were obtained after both beta- and alpha-adrenoceptors were blocked by propranolol and phentolamine. Losartan but not PD123177 caused parallel rightward shifts of the dose-response curve of angiotensin II for dP/dtmax in the aortic blood pressure controlled pithed rat without altering the maximal response. It is concluded that in the pithed rat angiotensin II produced an increase in myocardial contractile force which is not mediated by beta- or alpha-adrenoceptors. The inotropic effect appears to be mediated by angiotensin receptors, of the AT1-subtype.
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PMID:Positive inotropic action of angiotensin II in the pithed rat. 810 95

Microinjection of angiotensin II (ANG II) into the area postrema (AP) of urethan-anesthetized male Sprague-Dawley rats elicited statistically significant increases in mean arterial blood pressure at doses ranging from 10 pg to 500 ng (10 pg, mean +/- SE, 10.8 +/- 1.1 mmHg, P < 0.001; 250 ng, 15.2 +/- 2.6 mmHg, P < 0.001). Heart rate was also significantly increased at doses > 10 pg, although these increases were not dose dependent. Systemic administration of losartan (Dup-753), an AT1 antagonist, was able to significantly reduce the pressor response to 250 ng ANG (post-losartan: 81.9 +/- 9.5% reduction in blood pressure response, P < 0.0001), whereas PD123319, an AT2 antagonist, was without significant effect (P > 0.1). Microinjection of vasopressin (VP) (10 pg-500 ng) into the AP also resulted in statistically significant increases in blood pressure at doses ranging from 10 to 100 pg (10 pg, 7.0 +/- 1.5 mmHg, P < 0.05) and 100-500 ng (250 ng, 12.2 +/- 1.8 mmHg, P < 0.0001). Small but significant changes in heart rate were observed only at 100 pg and 100 ng. Systemic administration of a V1 antagonist significantly attenuated the increases in blood pressure in response to 50, 100, and 250 ng VP (250 ng, post-V1 antagonist: 66.4 +/- 8.6% reduction in blood pressure response, P < 0.001), whereas [desamino,D-Arg8]vasopressin (DDAVP), a V2 agonist, had a depressor effect when microinjected directly into the AP (250 ng, -9.9 +/- 1.6 mmHg, P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular consequences of microinjection of vasopressin and angiotensin II in the area postrema. 821 57

Angiotensin receptors are present in many tissue types, including adrenal cortex, renal glomeruli, heart, hypothalamus, liver, pancreas, pituitary, platelets, renal tubules, uterus and vascular smooth muscle. Two high-affinity receptor subtypes have been identified by radioligand binding with antagonists: losartan (DuP 753/MK954) identifies AT1 receptors; PD123177 and CGP42112A are markers for AT2 receptors. Angiotensin II may be produced locally in tissues outside the humoral system. For example, it is found in the brain, kidney and heart. Within the brain, the heptapeptide angiotensin(1-7) mimics some effects of angiotensin II, but may be formed directly from angiotensin I. Evidence for non-ACE-mediated angiotensin II production has been reported in the heart. Intravascular angiotensin II receptors are implicated in the central release of vasopressin and other hypophyseal hormones, in increasing sympathetic outflow, in the thirst response and, possibly, in cognitive function; in the inotropic and chronotropic effects of angiotensin II on the heart as well as in growth/hypertrophy; in the control of aldosterone release and in the balance between cortisol and aldosterone secretion; and in modulating sodium, chloride and bicarbonate transport within the kidney. Effects on the reproductive system, liver and pancreas have not been established. The pharmacological effects of angiotensin II antagonists will depend on their distribution characteristics as well as affinity for specific receptor subtypes. At present, however, the physiological role of AT2 receptors has not been defined.
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PMID:Role of angiotensin in the extravascular system. 823 88

The central actions of angiotensin II (ANG II) include the release of vasopressin (AVP) from the supraoptic nucleus (SON) via the pituitary gland into the blood. In conscious rats, we investigated whether catecholamines in the SON are involved in this release process. It was found that i.c.v. injections of ANG II (100 ng) selectively increased the release of norepinephrine (NA) from the SON. Like the ANG II i.c.v.-induced AVP release, this effect was prevented by i.c.v. pretreatment with the ANG II AT1 receptor antagonist, losartan (5 micrograms). The alpha-1 adrenoceptor antagonist, prazosin (0.7 nmol), injected bilaterally into the SON, significantly reduced the ANG II 100-ng i.c.v.-induced AVP release. Pretreatment with the alpha-2, beta-1 and beta-2 adrenoceptor antagonists, idazoxan, atenolol and ICI 118551, respectively, had no effect. Injections of NA into the SON increased plasma AVP at doses up to 10 nmol but not at higher doses (30-100 nmol). The effects of NA were mimicked by the alpha-1 adrenoceptor agonist, methoxamine (1-5 nmol). Bilateral pretreatment of the SON with losartan (5 micrograms) markedly inhibited the i.c.v. ANG II 100 ng-induced AVP release. The increase in AVP release after ANG II injections into the SON was also inhibited by losartan pretreatment into the SON, whereas prazosin had no effect. These results demonstrate that the ANG II-induced release of AVP is initiated through periventricular ANG II AT1 receptors and involves postsynaptic alpha-1 adrenoceptor stimulation in the SON. In addition, ANG II AT1 receptors in the SON can contribute to AVP release after periventricular ANG II receptor stimulation.
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PMID:Angiotensin II-induced vasopressin release is mediated through alpha-1 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus. 824 29

Intracerebroventricular (i.c.v.) administration of angiotensin II (ANG II) increases vascular resistance and arterial pressure by increasing the activity in the sympathetic nervous system (SNS-component) and secretion of vasopressin (VP-component). This study examined the role of AT1 and AT2 receptors in brain in mediating the exaggerated central cardiovascular effects of ANG II in conscious, adult (10 weeks) spontaneously hypertensive rats (SHR). Mean arterial pressure, heart rate and renal blood flow responses to intraventricular injection of ANG II (100 ng in 5 microliters) were determined 10 min after intraventricular administration of the AT1 receptor antagonist losartan alone (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand PD 123319 alone (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both ligands in combination. In control rats, intraventricular administration of losartan prevented the pressor and renal vascular resistance responses to intraventricular injection of ANG II, in a dose-dependent manner (P < 0.05), while intraventricular injection of PD 123319 was ineffective. Likewise, when the SNS- and VP-components were studied individually by preventing the VP-component with a V1 receptor antagonist (i.v.) or the SNS-component with chlorisondamine (i.v.), losartan (i.c.v.) prevented both components, while PD 123319 (i.c.v.) was without affect. In addition, doses of losartan, combined with 3.5 micrograms PD 123319, were no more effective in preventing the pressor or renal vascular resistance responses than losartan, administered alone, suggesting that the VP- and SNS-components of the pressor response to ANG II (i.c.v.) are mediated primarily by AT1 receptors in brain in conscious spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of blockade of AT1 and AT2 receptors in brain on the central angiotensin II pressor response in conscious spontaneously hypertensive rats. 833 21

In this article, we have discussed the localization of components of the renal renin-angiotensin system, as well as the existing information on the regulation of this axis and the effects of Ang II on renal function. All the components of the renin-angiotensin system are present in both fetal and adult kidney. In the adult kidney, renin is principally localized to jg cells of the distal afferent arteriole, where release is stimulated by increases in intracellular cAMP and inhibited by increases in cytosolic calcium. Four distinct stimuli mediating renin release are (1) NaCl sensed at the macula densa, (2) the sympathetic nervous system, (3) humoral factors, with Ang II, vasopressin, endothelin, and adenosine inhibiting renin release, and (4) changes in intrarenal blood pressure. Alterations in renal renin gene expression have been reported in pathophysiological states, such as salt depletion, diabetes mellitus, ureteral obstruction, Bartter's syndrome, and with high protein feeding. The highest renal concentrations of mRNA for the renin substrate angiotensinogen are found in the PT, where the protein is localized to subapical granules. Both salt depletion and androgens upregulate renal angiotensinogen mRNA. Of interest, renal angiotensinogen mRNA levels are lower in SHR than in normotensive WKY rats. As with angiotensinogen, renal ACE is mainly localized to the PT, with highest concentration on the brush border. The mechanisms of regulation of both renal angiotensinogen and ACE require further study. Using recently developed specific nonpeptide Ang II receptor antagonists, it appears that adult renal Ang II receptors are principally of the AT1 class, whereas fetal kidney Ang II receptors are of the AT2 subtype. By binding to AT1 receptors, Ang II exerts constrictive effects on both afferent and efferent arterioles, with increased effect reported on efferent arterioles. Glomerular Ang II receptors are localized to mesangial cells, mediating contractile responses resulting in changes in glomerular surface area and Kf, and potentially regulating mesangial sieving and phagocytosis. These receptors are reduced with salt restriction or in experimental diabetes. The highest concentrations of tubular Ang II receptors are found in PT, on both brush border and basolateral membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The intrarenal renin-angiotensin system. 843 83

Intracerebroventricular (i.c.v.) angiotensin II (ANG II) increases vascular resistance and elicits a pressor response characterized by sympathetic nervous system activation (SNS component) and increased vasopressin (VP) secretion (VP component). This study examines the role of brain AT1 and AT2 ANG II receptors in mediating the pressor and renal hemodynamic effects of i.c.v. ANG II in conscious Sprague-Dawley rats. Mean arterial pressure, heart rate and renal vascular resistance responses to i.c.v. ANG II (100 ng in 5 microliters) were determined 10 min after i.c.v. injection of either the AT1 receptor antagonist, DuP 753 (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand, PD 123319 (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. DuP 753 prevented the pressor response and the increase in renal vascular resistance that occurred following i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 was without affect. When the VP- and SNS components were studied individually, by preventing the SNS component with intravenous (i.v.) chlorisondamine or the VP component with a V1 receptor antagonist (i.v.) similar results were obtained; DuP 753 prevented the SNS component and significantly reduced the VP component. These results indicate that both central ANG II pressor components are mediated primarily by brain AT1 receptors. However, doses of DuP 753 were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05), suggesting that the pressor effects of i.c.v. ANG II may involve activation of multiple ANG II receptor subtypes.
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PMID:Functional role of brain AT1 and AT2 receptors in the central angiotensin II pressor response. 845 78


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