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)

2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4-yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulation of the phospoinositide signalling system and the angiotensin II-induced hypertrophy in aortic vascular smooth muscle cells of normotensive Wistar-Kyoto rats. 10(-7) M Losartan abolished the angiotensin II-induced formation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. 10(-6) M Losartan completely abolished the angiotensin II-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i). 10(-6) M Losartan lacked effects on the [Arg8]vasopressin-induced elevation of [Ca2+]i. In addition, 10(-6) M completely inhibited the angiotensin II-induced stimulation of Na+/H+ exchange in the vascular smooth muscle cells. 10(-10) to 10(-6) M Losartan inhibited the angiotensin II-induced cell protein synthesis in a concentration-dependent manner, yielding to an effective concentration (ED50) of 6.2 +/- 1.8 x 10(-8) M (n = 4). Losartan did not affect the platelet-derived growth factor-BB-induced increase in cell protein. These results show that Losartan is a highly specific angiotensin II receptor antagonist which inhibits angiotensin II-induced cell growth and thus may have beneficial effects on the development and regression of vascular hypertrophy.
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PMID:Losartan inhibits the angiotensin II-induced stimulation of the phosphoinositide signalling system in vascular smooth muscle cells. 142 30

In isolated rat hepatocytes PMA, angiotensin II and to a lesser extent other hormones induce an early genetic response (increased expression of c-fos, c-mos, c-myc and beta-actin) without altering the expression of the glyceraldehyde 3-phosphate dehydrogenase gene. PMA, PDB and O-met-PMA, but not alpha-phorbol, stimulated c-fos expression. The effect of angiotensin II was inhibited by the AT1 antagonist, Losartan (DuP 753) (Ki approx. 25 nM), but not by the AT2 antagonist PD123177. Angiotensin II was much more effective than vasopressin or epinephrine in inducing proto-oncogene expression which suggests that angiotensin II receptors may exert actions in addition to those shared with the receptors for the other calcium-mobilizing hormones. The effect of PMA and angiotensin II on c-fos expression took place rapidly, with half times of 7 and 12 min, respectively. Actinomycin D markedly diminished basal c-fos expression whereas cycloheximide had the opposite effect. Actinomycin D diminished the effect of PMA and angiotensin II but it did not block them. PMA and the calcium-mobilizing hormones increased c-fos expression above the level observed with cycloheximide alone. These data suggest that PMA and the calcium-mobilizing hormones increased both transcription of the c-fos gene and stabilization of the proto-oncogene mRNA.
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PMID:Angiotensin II and active phorbol esters induce proto-oncogene expression in isolated rat hepatocytes. 152 Jul 5

Angiotensin II (Ang II) given centrally produces an increase in blood pressure and motivation to drink. The physiological mechanisms that mediate the pressor response include release of vasopressin (AVP) and activation of the sympathetic nervous system. Using 2 new Ang II receptor antagonists, we were able to investigate the role of AT1 or AT2 receptors in mediating these effects. Adult male Sprague-Dawley rats were cannulated in the lateral ventricle and 5 days later catheterized in the carotid artery for blood pressure measurements. All experiments were carried out in conscious rats. Three treatments were given intraventricularly (i.v.t.), in 2 microliters artificial cerebrospinal fluid (ACSF) at 30 min intervals: (1) 50 ng Ang II, (2) 0.7 micrograms AT1 antagonist Losartan or 7.0 micrograms AT2 antagonist PD123177, followed by 50 ng Ang II, and (3) 50 ng Ang II, to test for recovery. Blood pressure and drinking measurements were recorded. Also, blood samples for assay of AVP were drawn at 1 or 3 min post-injection in 2 separate groups of rats. We found that both Losartan and PD123177 significantly reduced release of AVP to Ang II 1 min post-injection. Losartan significantly blocked the pressor response (P less than 0.001), while PD123177 had no significant effect. Drinking was also antagonized by Losartan (P less than 0.05) and reduced (n.s.) by PD123177. The results suggest that the pressor response to Ang II (i.v.t.) is predominantly AT1 mediated, while the drinking and AVP responses may be mediated by both receptor subtypes.
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PMID:The role of angiotensin, AT1 and AT2 receptors in the pressor, drinking and vasopressin responses to central angiotensin. 152 Nov 62

The effects of the nonpeptide angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on pressor responses to the selective alpha 1-adrenoceptor agonist cirazoline (10 ng/kg-3.0 mg/kg) in the pithed rat were compared. In addition, the effects of losartan and captopril on pressor responses to cirazoline were compared in the presence of the selective irreversible alpha 1-adrenoceptor antagonist SZL-49 (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5- dienyl-carbonyl)-piperzine) and/or the Ca2+ channel antagonist nifedipine. Losartan (5.0 mg/kg) and captopril (3.0 mg/kg), as compared to saline, significantly lowered the blood pressure of intact, anaesthetized and pithed rats. Continuous infusion with vasopressin was used to restore the blood pressure of pithed rats pretreated with losartan or captopril to a level comparable to animals that had received saline. Losartan, captopril, nifedipine (1.0 mg/kg), and SZL-49 (10.0 mg/kg) antagonized the pressor actions of cirazoline, which displaced the dose-diastolic blood pressure response curve for the agonist to the right. Moreover, pressor responses to cirazoline were significantly reduced in rats that had received losartan and nifedipine in comparison to nifedipine alone. In contrast, in rats treated with nifedipine, further administration of captopril did not significantly reduce pressor responses to cirazoline as compared to nifedipine alone. Cirazoline-mediated pressor responses at all doses were significantly attenuated in rats treated with SZL-49 and either losartan or nifedipine combined as compared to SZL-49 alone. In contrast, only cirazoline-mediated pressor responses at lower doses were significantly reduced by pretreatment with a combination of SZL-49 and captopril as compared to SZL-49 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of losartan and captopril on vasopressor actions of cirazoline in the absence and presence of SZL-49 and nifedipine. 756 55

The role of brain angiotensin II (ANG II) in mediating cardiovascular, vasopressin, and renin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto (WKY) and Wistar rats. Intracerebroventricular administration of losartan (10 micrograms) and saralasin (1 microgram.microliter-1.min-1) produced a markedly greater fall in blood pressure and a reduced tachycardia during and after hemorrhage (15 ml/kg) compared with the artificial cerebrospinal fluid control in SHR and Wistar rats but not in WKY rats. Vasopressin release after hemorrhage was also impaired, but renin release was enhanced by intracerebroventricular ANG II antagonists in SHR and Wistar rats but not in WKY rats. Losartan and saralasin produced remarkably similar effects on the cardiovascular, vasopressin, and renin responses to hemorrhage. These data suggest that brain ANG II acting through AT1 receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage. The relative importance of brain angiotensin system may vary in different strains of rate.
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PMID:Central ANG II-receptor antagonists impair cardiovascular and vasopressin response to hemorrhage in rats. 761 27

Stimulation of angiotensin II AT2 receptors has been shown to inhibit AT1 receptor-mediated actions in peripheral tissues. The role of AT2 receptors in the central actions of angiotensin is not well understood. In the present study, plasma vasopressin levels and water intake in response to intracerebroventricular angiotensin II (10 pmol) were determined after intracerebroventricular pretreatment with PD 123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetrahy dro-1H- imidazo[4,5-c]pyridine-6-carboxylic acid-2HCl), a selective AT2 receptor antagonist (10, 100 and 1000 pmol), or with losartan (2-n-butyl-4-chloro-5-hydroxy-methyl-1-2'-(1H-tetrazole-5-yl)biphenyl-4- yl)methylimidazole, potassium salt), a specific AT1 receptor antagonist (0.2, 2 and 10 nmol). Blood samples for vasopressin determination were drawn 90 s after angiotensin II injection and the drinking response was determined in a time interval of 10 min after intracerebroventricular angiotensin II. Losartan at a dose of 2 nmol or higher completely prevented vasopressin release and drinking response to angiotensin II. The drinking response was already attenuated after pretreatment with the lowest dose of losartan. In contrast, PD 123177 potentiated the angiotensin II-induced vasopressin release (39.7 +/- 2.7 pg/ml after 1000 pmol PD 123177 vs. 21.3 +/- 2.9 pg/ml in vehicle-pretreated controls, P < 0.05). The dipsogenic response to angiotensin II was also potentiated by PD 123177 (9.5 +/- 0.7 ml after 1000 pmol PD 123177 vs. 5.1 +/- 1.3 ml in vehicle-pretreated controls, P < 0.05). Our results suggest that the angiotensin II-induced vasopressin release and drinking, mediated by central AT1 receptors, are under inhibitory control by central AT2 receptors.
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PMID:Angiotensin AT1 receptor-mediated vasopressin release and drinking are potentiated by an AT2 receptor antagonist. 776 95

1. The effects of the beta 2-adrenoceptor agonist, procaterol, on sympathetic neuroeffector transmission were studied in the pithed adrenal demedullated rat to determine if generation of angiotensin II was involved in its effect. Pressor responses were elicited by either electrical stimulation (20 V, 2 Hz) of the entire spinal sympathetic outflow or methoxamine (0.1 mg kg-1, i.v.). 2. Sodium nitroprusside (3 and 5 micrograms kg-1 min-1, i.v.) produced hypotension and the pressor responses to both sympathetic nerve stimulation and methoxamine were reduced. This indicates that decreasing blood pressure in pithed rats reduces pressor responses. Procaterol (10 and 30 ng kg-1 min-1, i.v.) also produced hypotension but did not alter pressor responses to sympathetic nerve stimulation. Nevertheless, procaterol (10 and 30 ng kg-1 min-1, i.v.) did reduce pressor responses to to methoxamine. Together these results suggest that procaterol may have enhanced sympathetic neurotransmitter release. This was confirmed in another series of experiments where procaterol (30 ng kg-1 min-1, i.v.) increased plasma noradrenaline levels during sympathetic nerve stimulation. 3. Captopril (5 mg kg-1, i.v.) produced hypotension and as expected reduced pressor responses to sympathetic nerve stimulation. When the hypotensive effect of captopril was abolished by concomitant vasopressin infusion (1.5-4.5 i mu kg-1 min-1, i.v.), pressor responses to sympathetic nerve stimulation were restored to pre-captopril levels. In this situation procaterol (10 and 30 ng kg-' min', i.v.) reduced basal blood pressure and did not alter pressor responses to sympathetic nerve stimulation whereas the pressor responses were reduced by an equihypotensive infusion of sodium nitroprusside (3 and 5 jig kg-' min' , i.v.). The lack of reduction of pressor responses after procaterol in the presence of captopril is indirect evidence that procaterol may have enhanced noradrenaline release independently of angiotensin II.4. In another series of experiments, plasma noradrenaline levels elicited by sympathetic nerve stimulation were not altered by captopril (5 mg kg', i.v.). In the presence of captopril (5 mg kg-', i.v.),procaterol (30 ng kg- min-1, i.v.) no longer enhanced plasma noradrenaline levels during sympathetic nerve stimulation. However, since the dose of captopril is well above that required to block angiotens in converting enzyme (ACE) the effect may be non-specific. Therefore, the selective AT, receptor antagonist, losartan (10mgkg'1, i.v.), was also used. Losartan (10mgkg'1, i.v.) did not alter plasma noradrenaline levels during sympathetic nerve stimulation, and in the presence of losartan procaterol(30 ng kg-I min-', i.v.) enhanced plasma noradrenaline levels during sympathetic nerve stimulation. This result further suggests that 1-adrenoceptor facilitation of noradrenaline release from sympathetic nerves in the pithed rat occurs by a mechanism independent of angiotensin II generation.
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PMID:Facilitation by procaterol, a beta-adrenoceptor agonist, of noradrenaline release in the pithed rat independently of angiotensin II formation. 785 67

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

Losartan, a nonpeptide angiotensin II receptor antagonist, was used to establish the role of brain AT1 angiotensin II receptor subtype on the natriuretic, antidiuretic, and dipsogenic actions of centrally administered renin. Intracerebroventricular administration of renin reduces urine volume and increases sodium excretion and water intake in conscious, male, hydrated rats. Losartan (3 or 10 mg/kg, sc) reduced the increased sodium excretion and totally inhibited the antidiuretic action induced by intracerebroventricular renin. When both renin and Losartan were given intracerebroventricularly, at the highest dose, there was a potent inhibition of the antidiuretic and natriuretic actions. Peripheral and central administration of the AT1 receptor blocker significantly lengthened the onset of drinking behavior and reduced the cumulative water intake observed after intracerebroventricular injection of renin. Our results strongly suggest that the brain AT1 receptor subtype mediates the physiologic actions of angiotensin II, such as drinking behavior, the increase in sodium excretion, and vasopressin release.
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PMID:Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin. 845 3

Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominantly express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 microliters) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 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. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG-II-induced pressor effects may involve activation of multiple receptor subtypes.
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PMID:Functional roles of brain AT1 and AT2 receptors in the central angiotensin II pressor response in conscious young spontaneously hypertensive rats. 849 Oct 41


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