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

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.