Evidence for a new angiotensin-(1-7) receptor subtype in the aorta of Sprague-Dawley rats

We have recently described, in the mouse aorta, the vasodilator effect of angiotensin-(1-7) (Ang-(1-7)) was mediated by activation of the Mas Ang-(1-7) receptor and that A-779 and D-Pro(7)-Ang-(1-7) act as Mas receptor antagonists. In this work we show pharmacological evidence for the existence of a different Ang-(1-7) receptor subtype mediating the vasodilator effect of Ang-(1-7) in the aorta from Sprague-Dawley (SD) rats. Ang-(1-7) induced an endothelium-dependent vasodilator effect in aortic rings from SD rats which was inhibited by removal of the endothelium and by L-NAME (100 mu M) but not by indomethacin (10 mu M). The Ang-(1-7) receptor antagonist D-Pro(7)-Ang-(1-7) (0.1 mu M) abolished the vasodilator effect of the peptide. However, the other specific Ang-(1-7) receptor antagonist, A-779 in concentrations up to 10 mu M, did not affect vasodilation induced by Ang-(1-7). The Ang II AT(1) and AT(2) receptors antagonists CV11974 (0.01 mu M) and PD123319 (1 mu M), respectively, the brady-kinin B-2 receptor antagonist HOE 140 (1 mu M) and the inhibitor of ACE captopril (10 mu M) did not change the effect of Ang-(1-7). Our results show that in the aorta of SD rats, the vasodilator effect of Ang-(1-7) is dependent on endothelium-derived nitric oxide. This effect is mediated by the activation of Ang-(1-7) receptors sensitive to D-Pro(7)-Ang-(1-7), but not to A-779, which suggests the existence of a different Ang-(1-7) receptor subtype. (c) 2006 Elsevier Inc. All rights reserved.