Renin Angiotensin system (RAS) inhibition attenuates mitochondrial dysfunction, oxidant production and cardiac hypertrophy in Spontaneously Hypertensive Rats (SHR).

BARBARA PIOTRKOWSKI; ELENA MV DE CAVANAGH; OSVALDO R. KOCH; CESAR G FRAGA

Santa Barbara, California, Estados Unidos

Congreso; Oxygen Club of California World Congress; 2006

In previous work, we showed that RAS inhibition prevented the decay of mitochondrial function in kidneys of SHR, independently of blood pressure (BP) reduction. Here we studied whether a non-BP lowering dose of enalapril, an angiotensin converting enzyme inhibitor, could protect cardiac tissue and mitochondria from hypertension-related dysfunction. Three-month-old SHR received water containing enalapril (10 mg/kg/day, E) or no additions (S) for 5 months. Wistar-Kyoto rats (W) were normotensive controls. At the end of the study, BP was higher in E and S relative to W. In S, heart/body weight ratio was higher than in E and W. In S, but not in E and W, myocardiocytes were replaced by fibrotic tissue. Matrix metalloprotease activity was lower in E with respect to S and W. In S, mtNOS activity and eNOS expression and activity were lower compared to E and W. Mitochondrial membrane potential in E was lower than in S and W; and H2O2 production was higher in E and S compared to W. In S, Mn-SOD activity was higher than in E and W. NADH-dehydrogenase activity was lower in S and E than in W. In summary, in SHR enalapril protects from cardiac hypertrophy, and attenuates several parameters of cardiac mitochondria dysfunction, independently of its known effects on BP. Supported by ANPCyT 01-08951 (Argentina).