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The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of Mas-knockout mice

Item Type:Article
Title:The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of Mas-knockout mice
Creators Name:Lemos, V.S. and Silva, D.M. and Walther, T. and Alenina, N. and Bader, M. and Santos, R.A.
Abstract:Recently, we demonstrated that the endothelium-dependent vasodilator effect of angiotensin(1-7) in the mouse aorta is abolished by genetic deletion of the G protein-coupled receptor encoded by the Mas protooncogene. To circumvent the limitations posed by the possible metabolism of Ang(1-7) in this vessel, in this work we studied the mechanism underlying the vasorelaxant effect of AVE 0991, a nonpeptide mimic of the effects of Ang(1-7), using wild-type and Mas-deficient mice. Ang(1-7) and AVE 0991 induced an equipotent concentration-dependent vasodilator effect in aortic rings from wild-type mice that was dependent on the presence of endothelium. The vasodilator effect of Ang(1-7) and AVE 0991 was completely blocked by 2 specific Ang(1-7) receptor antagonists, A-779 and D-Pro7-Ang(1-7), and by inhibition of NO synthase with L-NAME. Moreover, in aortic rings from Mas-deficient mice, the vasodilator effect of both Ang(1-7) and AVE 0991 was abolished. In contrast, the vasodilator effect of acetylcholine and substance P were preserved in Mas-null mice. In addition, the vasoconstriction effect induced by Ang II was slightly increased, and the vasodilation induced by the AT2 agonist cGP 42112A was not altered in Mas-deficient mice. Our results show that Ang(1-7) and AVE 0991 produced an NO-dependent vasodilator effect in the mouse aorta that is mediated by the G protein-coupled receptor Mas.
Keywords:Ang(1-7) receptor, Angiotensin II, Angiotensin(1-7), AVE 0991, Mas receptor, Mouse aorta, Animals, Mice
Source:Journal of Cardiovascular Pharmacology
ISSN:0160-2446
Publisher:Lippincott Williams & Wilkins (U.S.A.)
Volume:46
Number:3
Page Range:274-279
Date:1 September 2005
PubMed:View item in PubMed

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