Reduced isoproterenol-induced renin-angiotensin changes and extracellular matrix deposition in hearts of TGR(A1–7)3292 rats

Abstract 

We investigated the expression of specific extracellular matrix (ECM) proteins in cardiac hypertrophy induced by isoproterenol in TGR(A1–7)3292 rats. Additionally, changes in circulating and tissue renin-angiotensin system (RAS) were analyzed. Left ventricles (LV) were used for quantification of collagen type I, III, and fibronectin using immunofluorescence-labeling techniques. Angiotensin (Ang) II levels were measured by radioimmunoassay. Expression of RAS components was assessed by semi-quantitative polymerase chain reaction (PCR) or real-time PCR. Isoproterenol treatment induced an increase in the expression of collagen I, III, and fibronectin in normal rats. Collagen I and fibronectin expression were decreased in TGR(A1–7)3292 at basal conditions and both proteins increased by isoproterenol treatment; however, the levels achieved were still significantly lower than those observed in treated normal rats. The increase in collagen III observed in normal rats was completely blunted in TGR(A1–7)3292. Moreover, TGR(A1–7)3292 presented lower Ang II levels and angiotensinogen expression and a higher angiotensin-converting enzyme 2 (ACE2) expression in LV. Isoproterenol treatment increased cardiac Ang II concentration only in normal rats, which was associated with an increase in ACE2 and a decrease in Mas expression. These observations suggest that Ang-(1–7) specifically modulates the expression of RAS components and ECM proteins in LV.

Keywords: Mas receptor, ACE2, collagen, hypertrophy