The aim of the present study was to investigate the coronary effects of Ang-(1–7) [angiotensin-(1–7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1–7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (NG-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1–7) in control hearts. The coronary vasodilation produced by Ang-(1–7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1–7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1–7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1–7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1–7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1–7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1–7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.
Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts
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Álvaro P. S. Souza, Deny B. S. Sobrinho, Jônathas F. Q. Almeida, Gisele M. M. Alves, Larissa M. Macedo, Juliana E. Porto, Eneida F. Vêncio, Diego B. Colugnati, Robson A. S. Santos, Anderson J. Ferreira, Elizabeth P. Mendes, Carlos H. Castro; Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts. Clin Sci (Lond) 1 November 2013; 125 (9): 449–459. doi: https://doi.org/10.1042/CS20120519
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