Abstract 428: Complete Blockade of the Vasorelaxant Effects of Ang-(1-7) and Bradykinin in Murine Microvessels by Antagonists of the Receptor Mas
The heptapeptide angiotensin-(1-7) is a biologically active metabolite of angiotensin II, the predominant peptide of the renin-angiotensin system. Recently, we have shown that the receptor Mas is associated with angiotensin-(1-7)-induced signalling and mediates, at least in part, the vasodilatory properties of angiotensin-(1-7). However, it remained controversial whether an additional receptor can account for angiotensin-(1-7)-induced vasorelaxation. Here, we used two different angiotensin-(1-7) antagonists, A779 or D-Pro-angiotensin-(1-7), to address this question. We also studied the influence of both antagonists on the vasodilatation induced by bradykinin. Isolated mesenteric microvessels from both wild-type and Mas deficient C57Bl/6 mice were pre-contracted with norepinephrine, and vascular reactivity to angiotensin-(1-7) and bradykinin was subsequently studied using a small vessel myograph. Both peptides, angiotensin-(1-7) and bradykinin, triggered a concentration-dependent vasodilation in wild-type microvessels, that was totally absent in the presence of the nitric oxide synthase inhibitor ω-nitro-L-arginine methyl ester (L-NAME). In these vessels, the pre-incubation with the Mas antagonists A779 or D-Pro-angiotensin-(1-7) totally abolished vasodilatatory capacity of both angiotensin-(1-7) and bradykinin, which was nitric oxide-mediated. Accordingly, Mas deficient microvessels lacked the capacity to relax in response to either angiotensin-(1-7) or bradykinin. In murine microvessels, the angiotensin-(1-7) antagonists A779 and D-Pro-angiotensin-(1-7) equally block a receptor, which mediates the complete angiotensin-(1-7)-induced vasodilation in mesenteric microvessels. Importantly, beyond mediating the vascular actions of angiotensin-(1-7), Mas appears to be also a critical player in NO-mediated vasodilation induced by renin-angiotensin system-independent agonists.
- © 2012 by American Heart Association, Inc.