Angiotensin II Type 1 receptor blockade restores angiotensin-(1-7)-induced coronary vasodilation in hypertrophic rat hearts

The purpose of this study was to investigate the coronary effects of angiotensin (Ang)-(1-7) in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta coarctation (CoA). 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 Mas receptor antagonist A-779. Pretreatment with L-NAME or ODQ (nitric oxide synthase and soluble guanylate cyclase inhibitor, 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 antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not 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 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 pretreatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which w...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research