Angiotensin (1-7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5/6...

The renin-angiotensin system (RAS) plays a critical role in chronic renal failure associated with heart failure. In the past few years, angiotensin (Ang) (1-7) have been reported to counteract the effects of angiotensin II (Ang II) and were even considered as a new therapeutical target in RAS. The purposes of this study were to examine whether the Ang (1-7) improves the heart function and remodeling of the left ventricle (LV) in mice with 5/6 nephrectomy (NC). We used a 5/6 nephrectomy to induce significant renal dysfunction in wildtype mice (WT). Twelve weeks after NC, WT showed high blood pressure, significant left-ventricular dilation and dysfunction, which were accompanied by cardiomyocyte hypertrophy, diffuse interstitial fibrosis and oxidative damage of cardiomyocytes. Exogenous Ang (1-7) injection improved the heart function and remodeling of LV in mice with 5/6 NC accompanied by a reduction in cardiac interstitial fibrosis, inflammatory cytokine expression and oxidative damage levels of cardiomyocytes, decrease in the profibrotic signaling molecule transforming growth factor (TGF)-beta and increase in the collagen degradation signaling molecule matrix metalloproteinase (MMP)-2, -9. However, these beneficial effects did not occur in hydralazine-treated mice. These findings suggest that (1) Exogenous Ang (1-7) injection improve the heart function and remodeling of LV in mice with 5/6 NC. (2) These beneficial effects are independent of its anti-blood pressure effect.