Journal
HYPERTENSION
Volume 62, Issue 5, Pages 920-926Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.112.00762
Keywords
angiotensin II; blood pressure; compound 21; receptor; angiotensin; type 1; receptor; angiotensin; type 2; renal circulation
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Funding
- Research council of the Vrije Universiteit Brussel
- Flemish Research Fund
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Angiotensin II type 2 receptor (AT(2)R)-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 AT(2)R 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 AT(2)R 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 D-1 receptor agonist fenoldopam, used as positive control, reduced blood pressure and renal vascular resistance in both strains. The AT(2)R antagonist PD123319 and the nitric oxide synthase inhibitor L-NMMA (N-G-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 AT(2)R stimulation in vivo, mediated by nitric oxide and partially by prostaglandins. AT(2)R may have a pathophysiological role to modulate renal hemodynamic effects of angiotensin II in the hypertensive state.
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