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Evidence for a functional interaction of the angiotensin-(1-7) receptor Mas with AT1 and AT2 receptors in the mouse heart

Item Type:Article
Title:Evidence for a functional interaction of the angiotensin-(1-7) receptor Mas with AT1 and AT2 receptors in the mouse heart
Creators Name:de Castro, C.H. and Souza dos Santos, R.A. and Ferreira, A.J. and Bader, M. and Alenina, N. and de Almeida, A.P.
Abstract:The aim of this study was to evaluate the angiotensin (Ang)-(1–7) effects in isolated mouse hearts. The hearts of male C57BL/6J and knockout mice for the Ang-(1–7) receptor Mas were perfused by the Langendorff method. After a basal period, the hearts were perfused for 20 minutes with Krebs-Ringer solution (KRS) alone (control) or KRS containing Ang-(1–7) (0.22 pmol/L), the Mas antagonist A-779 (115 nmol/L), the angiotensin type 1 receptor antagonist losartan (2.2 μmol/L), or the angiotensin type 2 receptor antagonist PD123319 (130 nmol/L). To evaluate the involvement of Ang receptors, prostaglandins, and nitric oxide in the Ang-(1–7) effects, the hearts were perfused for 20 to 30 minutes with KRS containing either A-779, losartan, PD123319, indomethacin, or NG-nitro-l-arginine methyl ester (l-NAME) alone or in association with subsequent Ang-(1–7) perfusion. In addition, hearts from Mas-knockout mice were perfused for 20 minutes with KRS containing Ang-(1–7) (0.22 pmol/L) and losartan. Ang-(1–7) alone did not change the perfusion pressure. Strikingly, in the presence of losartan, 0.22 pmol/L Ang-(1–7) induced a significant decrease in perfusion pressure, which was blocked by A-779, indomethacin, and l-NAME. Furthermore, this effect was not observed in Mas-knockout mice. In contrast, in the presence of PD123319, Ang-(1–7) produced a significant increase in perfusion pressure. This change was not modified by the addition of A-779. Losartan reduced but did not abolish this effect. Our results suggest that Ang-(1–7) produces complex vascular effects in isolated, perfused mouse hearts involving interaction of its receptor with angiotensin type 1- and type 2-related mechanisms, leading to the release of prostaglandins and nitric oxide.
Keywords:Angiotensin Receptors, Cardiac Function, Heart, Angiotensin Antagonist, Prostaglandins, Animals, Mice
Publisher:American Heart Association
Page Range:937-942
Date:12 September 2005
Official Publication:https://doi.org/10.1161/01.HYP.0000175813.04375.8a
PubMed:View item in PubMed

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