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 μM) but not by indomethacin (10 μM). The Ang-(1–7) receptor antagonist D-Pro 7-Ang-(1–7) (0.1 μM) abolished the vasodilator effect of the peptide. However, the other specific Ang-(1–7) receptor antagonist, A-779 in concentrations up to 10 μM, did not affect vasodilation induced by Ang-(1–7). The Ang II AT 1 and AT 2 receptors antagonists CV11974 (0.01 μM) and PD123319 (1 μM), respectively, the bradykinin B 2 receptor antagonist HOE 140 (1 μM) and the inhibitor of ACE captopril (10 μM) 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.