Avaliação da Cardioproteção em Ratos que Superexpressam uma Proteína de Fusão Produtora de Angiotensina-(1-7) [TGR(A1-7)3292]

Abstract

Angiotensin-(1-7) (Ang-(1-7) is now considered to be a biologically active member of the renin-angiotensin system. The functions of Ang-(1-7) are often opposite to those attributed to the main effector component of the renin-angiotensin system, Ang II. Recently it has been suggested that Ang-(1-7) has cardioprotective properties. In the present study, we investigated the effect of Ang-(1-7) on cardiac hypertrophy. Heart hypertrophy was induced in male Sprague-Dawley (SD) and TG rats [TGR(A-7)3292] by daily injection of isoproterenol (2 mg/Kg i.p, 7 days). Control groups received daily injection of vehicle (0.9 % NaCl 0.1 ml/100g i.p, 7 days). At the end of the 7-day period, the rats were killed by decaptation and the heart and blood were immediately collected. The atria and right ventricle were dissected. Wet weights of the left ventricles were recorded and normalized for body weight. The left ventricles were used for morphometric analyzes and quantification of collagen I, III and fibronectin proteins by immunofluorescence using confocal microscopy. Angiotensins were determined by radioimmunoassay (RIA) in plasma and left ventricles. In addition, atrial natriuretic peptide was also determined by RIA in the plasma. The isoproterenol-induced hypertrophy was attenuated in TG rats. The expression of collagen I, III and fibronectin proteins in the extracellular matrix were also attenuated in isoproterenol-treated TG rats left ventricles. Expression of left ventricle angiotensinogen, ACE2, collagen I, III, Mas and AT1 receptors mRNA levels were assessed by semi-quantitative polymerase chain reaction. The cardiac Ang II level was significantly decreased in the TG rats. In contrast, the plasma Ang II levels were significantly increased in TG animals .Angiotensiogen mRNA in the left ventricle was significantly decreased in TG rats while ACE2 mRNA was significantly increased in TG rats. No significant changes were observed for Mas receptor mRNA levels and AT1 receptor mRNA levels in the left ventricles of TG rats. A significant increase of plasma ANP concentration was observed in TG rats. Isoproterenol did not change the biochemical alterations observed in the TG rats before the treatment . These results reinforce the hypothesis that Ang-(1-7) plays an important site-specific role within renin-angiotensin system and others peptidic systems.