Standard

Harvard

APA

Vancouver

Author

BibTeX

@article{aa69d844c8fb4dfe8a0dc0a9fee9e39c,
title = "Angiotensin II type 2 receptor-mediated and nitric oxide - Dependant renal vasodilator response to compound 21 unmasked by angiotensin-converting enzyme inhibition in spontaneously hypertensive rats in vivo.",
abstract = "Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated in different vascular beds in vitro and in perfused organs. In vivo studies, however, consistently failed to disclose renal vasodilator responses to compound 21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade. Here, we investigated in vivo whether angiotensin-converting enzyme inhibition, reducing endogenous angiotensin II levels, could unmask the effects of selective AT2R stimulation on blood pressure and renal hemodynamics in normotensive and hypertensive rats. After pretreatment with the angiotensin-converting enzyme inhibitor captopril, intravenous administration of compound 21 did not affect blood pressure and induced dose-dependent renal vasodilator responses in spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains. The AT2R antagonist PD123319 and the nitric oxide synthase inhibitor L-NMMA (NG-monomethyl-L-arginine acetate) abolished the renal vasodilator response to compound 21 without affecting responses to fenoldopam. The cyclooxygenase inhibitor indomethacin partially inhibited the renal vascular response to compound 21, whereas the bradykinin B2 receptor antagonist icatibant was without effect. Angiotensin-converting enzyme inhibition unmasked a renal vasodilator response to selective AT2R stimulation in vivo, mediated by nitric oxide and partially by prostaglandins. AT2R may have a pathophysiological role to modulate renal hemodynamic effects of angiotensin II in the hypertensive state.",
keywords = "angiotensin II, blood pressure, compound 21",
author = "Sofie Brouwers and Smolders, {Ilse Julia} and Ann Massie and Alain Dupont",
year = "2013",
month = "10",
day = "16",
language = "English",
volume = "62",
pages = "920--926",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",

}

RIS

TY - JOUR

T1 - Angiotensin II type 2 receptor-mediated and nitric oxide - Dependant renal vasodilator response to compound 21 unmasked by angiotensin-converting enzyme inhibition in spontaneously hypertensive rats in vivo.

AU - Brouwers, Sofie

AU - Smolders, Ilse Julia

AU - Massie, Ann

AU - Dupont, Alain

PY - 2013/10/16

Y1 - 2013/10/16

N2 - Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated in different vascular beds in vitro and in perfused organs. In vivo studies, however, consistently failed to disclose renal vasodilator responses to compound 21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade. Here, we investigated in vivo whether angiotensin-converting enzyme inhibition, reducing endogenous angiotensin II levels, could unmask the effects of selective AT2R stimulation on blood pressure and renal hemodynamics in normotensive and hypertensive rats. After pretreatment with the angiotensin-converting enzyme inhibitor captopril, intravenous administration of compound 21 did not affect blood pressure and induced dose-dependent renal vasodilator responses in spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains. The AT2R antagonist PD123319 and the nitric oxide synthase inhibitor L-NMMA (NG-monomethyl-L-arginine acetate) abolished the renal vasodilator response to compound 21 without affecting responses to fenoldopam. The cyclooxygenase inhibitor indomethacin partially inhibited the renal vascular response to compound 21, whereas the bradykinin B2 receptor antagonist icatibant was without effect. Angiotensin-converting enzyme inhibition unmasked a renal vasodilator response to selective AT2R stimulation in vivo, mediated by nitric oxide and partially by prostaglandins. AT2R may have a pathophysiological role to modulate renal hemodynamic effects of angiotensin II in the hypertensive state.

AB - Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated in different vascular beds in vitro and in perfused organs. In vivo studies, however, consistently failed to disclose renal vasodilator responses to compound 21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade. Here, we investigated in vivo whether angiotensin-converting enzyme inhibition, reducing endogenous angiotensin II levels, could unmask the effects of selective AT2R stimulation on blood pressure and renal hemodynamics in normotensive and hypertensive rats. After pretreatment with the angiotensin-converting enzyme inhibitor captopril, intravenous administration of compound 21 did not affect blood pressure and induced dose-dependent renal vasodilator responses in spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains. The AT2R antagonist PD123319 and the nitric oxide synthase inhibitor L-NMMA (NG-monomethyl-L-arginine acetate) abolished the renal vasodilator response to compound 21 without affecting responses to fenoldopam. The cyclooxygenase inhibitor indomethacin partially inhibited the renal vascular response to compound 21, whereas the bradykinin B2 receptor antagonist icatibant was without effect. Angiotensin-converting enzyme inhibition unmasked a renal vasodilator response to selective AT2R stimulation in vivo, mediated by nitric oxide and partially by prostaglandins. AT2R may have a pathophysiological role to modulate renal hemodynamic effects of angiotensin II in the hypertensive state.

KW - angiotensin II

KW - blood pressure

KW - compound 21

M3 - Article

VL - 62

SP - 920

EP - 926

JO - Hypertension

JF - Hypertension

SN - 0194-911X

ER -

ID: 2351674