Combination of angiotensin-(1–7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy

We recently found that overexpression of angiotensin (Ang)-converting enzyme 2, which metabolizes Ang-II to Ang-(1-7) and Ang-I to Ang-(1-9), may improve left ventricular remodeling in diabetic cardiomyopathy. Here we aimed to test whether chronic infusion of Ang-(1-7) can dose-dependently ameliorate left ventricular remodeling and function in a rat model of diabetic cardiomyopathy and whether the combination of Ang-(1-7) and Ang-converting enzyme inhibition may be superior to single therapy. Our results showed that Ang-(1-7) treatment dose-dependently ameliorated left ventricular remodeling and dysfunction in diabetic rats by attenuating myocardial fibrosis, myocardial hypertrophy and myocyte apoptosis via both the Mas receptor and angiotensin II type 2 receptor. Furthermore, combining Ang-(1-7) with perindopril provided additional cardioprotection relative to single therapy. Ang-(1-7) administration provides a novel and promising approach for treatment of diabetic cardiomyopathy.