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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine neuroblastoma N1E-115 cell line possesses a high density of angiotensin II (AngII) receptors that can be solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. These solubilized binding sites exhibited high affinity for CGP-42112A and not Losartan, indicating that they were of the AT2 subtype. However, displacement of 125I-AngII with the AT2 nonpeptide antagonist PD-123319 resulted in a biphasic curve, suggesting heterogeneity of the AT2 receptor population in N1E-115 cells. In support of this view, separation of two receptor populations was accomplished with heparin-Sepharose chromatography. More specifically, three distinct protein peaks eluted from the heparin-Sepharose column, two of which bound 125I-AngII with high affinity and saturability. One of these binding peaks (peak I) eluted rapidly and represented approximately 80% of the total binding activity, whereas the remaining binding activity was contained within a second peak (peak III) that required the addition of 1.5 M NaCl for its complete elution. Pharmacological analysis revealed that both peaks of binding activity were exclusively AT2 receptors insofar as they exhibited high affinity for CGP-42112A and little or no affinity for the AT1-selective antagonist Losartan. However, whereas the nonpeptidic AT2-selective antagonist PD-123319 completely displaced the binding of 125I-AngII from peak I in a monophasic fashion (IC50 = 9.1 +/- 4.1 nM; mean +/- SEM; n = 3), PD-123319 was much less effective in displacing 125I-AngII from peak III (IC50 = 196 +/- 27 nM; mean +/- SEM; n = 3). Treatment of individual peaks with the reducing agent dithiothreitol caused a large increase in 125I-AngII specific binding in peak III, whereas a decrease in binding was observed in peak I. Moreover, GTP gamma S significantly reduced high-affinity agonist binding in peak I but not peak III, further suggesting heterogeneity in the AT2 receptor family. Finally, immunoblotting studies with polyclonal antisera raised against peak I specifically detected two proteins of 110 and 66 kDa, as is true in crude solubilized membranes, whereas no immunospecific proteins were detected in peak III. These same antisera immunoprecipitated 125I-AngII binding activity in peak I but were ineffective in peak III. Collectively, these results suggest that heparin-Sepharose chromatography can efficiently separate two pharmacologically, biochemically and immunologically distinct populations of AT2 receptors.
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PMID:Biochemical characterization of two distinct angiotensin AT2 receptor populations in murine neuroblastoma N1E-115 cells. 818 20

Intracerebroventricular 100,000 pmol losartan (an AT1-receptor blocker) inhibited the initial drinking response of Wistar rats to 1 ml 2 M NaCl given subcutaneously but the intake over 3 h was not significantly inhibited. The same dose of the AT2-receptor blocker PD123319 had a more long-lasting inhibitory effect. Rats of three different strain, Wistar, Wistar-Kyoto (WK), and SH (spontaneously hypertensive), were subjected to sodium depletion using frusemide and a low-sodium diet; in the 3 h after 1.8% NaCl was made available, the intakes were 11.6 +/- 1.7 (SEM), 4.1 +/- 1.2 and 12.4 +/- 1.3 ml, respectively; water intakes in the same period averaged 4.2 +/- 1.1, 5.0 +/- 1.1 and 8.3 +/- 1.8 ml. The intake of both fluids by Wistar rats was not significantly affected by either losartan or PD123319. The intake of both saline and water in SHR rats was reduced by losartan. In evaluating the effect of antagonists to angiotensin II on the intake of water and NaCl in response to perturbations of hydromineral balance, difference in the route of administration of the stimulus and strain of the animals used must therefore be taken into account.
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PMID:The effect of losartan on drinking and NaCl intake in the rat in response to hyperosmotic and hypovolaemic stimuli: effect of route of administration and strain of rat. 889

Angiotensin II facilitates epinephrine release during insulin-induced hypoglycemia, and this effect appears to be independent of type 1 angiotensin II (AT1) receptors in man. In the present study, we hypothesized that the action of angiotensin II on adrenomedullary epinephrine release is mediated by an AT2 receptor-dependent mechanism. In conscious chronically instrumented rats, we measured plasma concentrations of catecholamines during acute insulin-induced hypoglycemia in groups of rats pretreated with the AT1 receptor antagonist losartan (10 mg/kg i.v.), the AT2 receptor antagonist PD123319 (30 mg/kg i.v.), combined losartan + PD123319, the converting enzyme inhibitor enalapril (1 mg/kg i.v.), or vehicle. In vehicle-treated rats, the area under the curve for changes in plasma epinephrine concentration [AUC(plasma epinephrine)] during insulin-induced hypoglycemia was 111+/-8 nmolXh/L (+/-SEM). Pretreatment with losartan alone did not affect AUC(plasma epinephrine) (113+/-17 nmol x h/L), while pretreatment with PD123319 tended to reduce the response (87+/-10 nmol x h/L; P=.08 versus vehicle). However, AUC(plasma epinephrine) was significantly reduced in rats that were pretreated with combined losartan + PD123319 (68+/-5 nmol x h/L; P<.001 versus vehicle) or enalapril: 86+/-10 nmol x h/L (P<.05 versus vehicle). Thus, combined treatment with losartan + PD 123319 proved more effective in attenuating the reflex increase in plasma epinephrine concentration during hypoglycemia than either of the two AT receptor antagonists given alone. We speculate that angiotensin II through binding to both receptor subtypes facilitates the sympathoadrenal reflex response by actions at several anatomical levels of the neural pathways involved in the sympathoadrenal reflex response elicited during insulin-induced hypoglycemia.
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PMID:AT1 and AT2 receptor blockade and epinephrine release during insulin-induced hypoglycemia. 945 33

Angiotensin II (AT2) has been implicated in the growth and/or differentiation of its target tissues. In the present study, testicular AT2 receptor and its subtypes in hypophysectomized rats were examined using quantitative in vitro autoradiography and Northern blot analysis in an attempt to determine possible involvement of pituitary hormones in their expression. Prepubescent (3 weeks of age) male Sprague-Dawley rats underwent hypophysectomy or sham operation. From 10 days thereafter, they were treated with vehicle, growth hormone, human chorionic gonadotrophin or human menopausal gonadotrophin for 10 days. Testicular AT2 receptors were labelled with 125I-[Sar1,Ile8] AT2 and differentiated into its subtypes (AT1 and FAT2) according to their susceptibility to AT1 (losartan, 5 microM) and AT2 (CGP42112B, 1 microM) antagonists. Hypophysectomy led to a marked increase in AT2 receptor concentration (sham-operated rats: 0.7 +/- 0.2 fmol/mg protein, hypophysectomized rats: 2.5 +/- 0.6 fmol/mg protein, mean +/- SEM, n = 11-12, p < 0.01) with predominant occurrence of AT1 receptors. Both human chorionic gonadotrophin and human menopausal gonadotrophin decreased testicular AT2 receptor concentration, whereas growth hormone did not affect AT2 receptor expression. Northern blot analysis revealed both testicular AT1 and AT2 receptor mRNA expression to be significantly increased after hypophysectomy and reduced by gonadotrophin treatment. These results suggest that the expression of testicular AT2 receptors is regulated by pituitary gonadotrophins and that AT2 may play a role in testicular growth and/or differentiation.
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PMID:Pituitary-dependent expression of the testicular angiotensin II receptor and its subtypes in rats. 974 47

The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2 (AT2) to angiotensin II-induced changes in collagen secretion and production were studied using the specific angiotensin receptor AT1 and AT2 antagonists telmisartan and P-186. The role of the renin-angiotensin system and its interaction with transforming growth factor-beta 1 (TGF-beta 1) in collagen deposition in cardiac fibroblasts in relation to the development of myocardial fibrosis is also discussed. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated in the presence of angiotensin II (ANG II) in a concentration range of 10(-10)-10(-6) M in serum-free Dulbecco's MEM medium for 24 h. Collagen production and secretion were assayed by [3H]-proline incorporation and noncollagen production and secretion were also analyzed. ANG II dose-dependently increased collagen secretion and production in rat adult cardiac fibroblasts in culture. Noncollagen secretion and production were also concentration-dependently increased by ANG II. Addition of 100 nmol/l ANG II increased (p < 0.01) collagen secretion and production by 75 +/- 6 (SEM) and 113 +/- 23%, respectively, and noncollagen secretion and production by 65 +/- 6 and 57 +/- 16%, respectively. Pretreatment of cardiac fibroblasts with telmisartan completely blocked the ANG II-induced increase in collagen secretion (p < 0.001) and production (p < 0.05) and in noncollagen secretion (p < 0.01) and production (p < 0.01). P-186 had no effect on the ANG II-induced increase in collagen secretion and production. Addition of telmisartan and P-186 did not affect collagen secretion and production in basal cardiac fibroblasts. TGF-beta 1 also concentration- and time-dependently increased the secretion and production of collagen in cardiac fibroblasts. Our data demonstrate that the effects of ANG II on collagen secretion and production in adult rat cardiac fibroblasts in culture are AT1-receptor mediated since they were abolished by the specific AT1-receptor antagonist telmisartan but not by the specific AT2-receptor antagonist P-186. The ability of ANG II to induce collagen synthesis in cardiac fibroblasts may be mediated by increased TGF-beta 1 production.
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PMID:Induction of cardiac fibrosis by angiotensin II. 1134 91

The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2 (AT2) to angiotensin II (Ang II)-induced changes in collagen secretion and production were studied using the specific angiotensin AT1- and AT2-receptor antagonists telmisartan and P-186, respectively. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated in the presence of 10(-10) to 10(-6) M Ang II in serum-free Dulbecco's MEM medium for 24 hours. Collagen production and secretion were assayed by'H-Proline incorporation; non-collagen production and secretion were also calculated. Ang II dose-dependently increased collagen secretion and production in rat adult cardiac fibroblasts in culture. Non-collagen secretion and production were also concentration-dependently increased by Ang II. Addition of 100 nmol/l Ang II increased (p<0.01) collagen secretion and production bv 75+/-6 (SEM)% and 113+/-23%, respectively, and non-collagen secretion and production by 65+/-6% and 57+/-16%, respectively. Pretreatment of cardiac fibroblasts with telmisartan completely blocked the Ang II-induced increase in collagen secretion (p<0.001) and production(p<0.05) and in non-collagen secretion (p<0.01) and production (p<0.01). P-186 had no effect on the Ang II-induced increase in collagen secretion and production. Addition of telmisartan and P-186 did not affect collagen secretion and production in basal cardiac fibroblasts. Our data demonstrate that the effects of Ang II on collagen secretion and production in adult rat cardiac fibroblasts in culture are AT1-receptor mediated, since they were abolished by the specific AT1-receptor antagonist, telmisartan, but not by the specific AT2-receptor antagonist, P-186.
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PMID:Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors. 1188 Nov 10

We investigated the effect of angiotensin II on intracellular cyclic GMP content and neurite outgrowth as an indicator of cell differentiation in PC12 W cells. Neurite outgrowth was examined by phase-contrast microscopy. Outgrown neurites were classified as small, medium and large, and were expressed as neurites per 100 cells. Angiotensin II (10-7 m) increased the outgrowth of medium and large neurites by mean +/- SEM 20.2 +/- 2.3 and 6.6 +/- 1.4 compared with 1.66 +/- 0.5 and 0.1 +/- 0.06 neurites per 100 cells in control. Cellular cyclic GMP content increased by 50-250% with angiotensin II at concentrations of 10-6-10-4 m. Both blockade of AT2 receptors and of nitric oxide synthase markedly reduced angiotensin II-induced neurite outgrowth and cyclic GMP production. In contrast, B2 receptor blockade had no effect or even increased these angiotensin II effects. Sodium nitroprusside and 8-bromo-cyclic GMP both mimicked the effects of angiotensin II on cell differentiation. The protein kinase G inhibitor KT-5823 inhibited the neurite outgrowth induced by both angiotensin II and 8-bromo-cyclic GMP. Our results demonstrate that angiotensin II can stimulate cell differentiation in PC12 W cells by nitric oxide-related and cyclic GMP-dependent mechanisms. The effects of angiotensin II on cell differentiation and cyclic GMP production were mediated via the AT2 receptor and further enhanced by bradykinin B2 receptor blockade.
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PMID:Contribution of bradykinin and nitric oxide to AT2 receptor-mediated differentiation in PC12 W cells. 1269 2

The role of the renin-angiotensin system (RAS) in regulating newborn mean arterial blood pressure (MAP) and tissue blood flow remains unclear. Although postnatal MAP increases, vascular responsiveness to infused angiotensin II (ANG II) is unchanged, possibly reflecting increased metabolic clearance rate of ANG II (MCR(ANG II)). To address this, we examined MAP, heart rate, plasma ANG II and renin activity (PRA), and MCR(ANG II) in conscious postnatal sheep (n = 9, 5-35 d old) before and during continuous systemic ANG II infusions to measure MCR (ANG II). Postnatal MAP increased (p < 0.02), whereas plasma ANG II decreased from 942 +/- 230 (SEM) to 471 +/- 152 and 240 +/- 70 pg/mL at <10 d, 10-20 d, and 21-35 d postnatally (p = 0.05), respectively. Despite high plasma ANG II, PRA remained elevated, averaging 6.70 +/- 1.1 ng/mL.h throughout the postnatal period, but decreased 35% (p = 0.01) during ANG II infusions. MCR(ANG II) decreased approximately sixfold after birth and averaged 115 mL/min.kg during the first month. Circulating ANG II is markedly increased after birth, reflecting placental removal, high fetal MCR(ANG II), and enhanced RAS activity. Although circulating ANG II decreases as MAP increases, MCR(ANG II) is unchanged, suggesting decreased ANG II production. Persistent vascular smooth muscle (VSM) AT2 receptor subtype (AT2R) expression after birth may modify the hypertensive effects of ANG II postnatally.
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PMID:The renin-angiotensin system in conscious newborn sheep: metabolic clearance rate and activity. 1742 51