Efeitos da rosuvastatina e olmesartana sobre o remodelamento de aorta, miocárdio e rim em ratos hipertensos por deficiência crônica da síntese de óxido nítrico

Abstract

Changes in myocardial remodeling, vascular inflammation, proteinuria, and glomerular inflammation in nitric oxide (NO)-deficient rats, treated with olmesartan medoxomil (OLM) and / or rosuvastatin calcium (ROS) were studied after 28 days in order to assess the impact of these drugs. Vehicle (G1), nitro-L-arginine methyl ester (L-NAME) 30mg/kg/dia (G2), OLM 5mg/kg/day (G3), ROS 20mg/kg/day (G4), OLM 0,5mg/kg/day (G5), ROS 2mg/kg/day (G6), OLM 0.5+ROS 2mg/kg/day (G7), OLM 5+ROS 20mg/kg/day (G8) orally administered to Wistar rats. Systolic pressure (SBP) measured weekly. Haematological, biochemical {total cholesterol (TC), triglycerides (Tg), aminotransferase (AMT), alkaline phosphatase (ALP), creatinine (Cr), nitrite / nitrate (NOx), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFα)}, urinary {albumin / creatinine ratio (UACR)}. Cuts from the left ventricle, aorta, kidneys (hematoxylin / eosin and Masson) were morphometrically analyzed: crosssectional area of cardiomyocytes (Acmy), intima-media thickness on the arterial lumen (IMT), perivascular fibrosis of intramyocardial arterioles ratio (PFR). Glomerular macrophages (GM) were analyzed by immunohistochemistry. L-NAME increased the SBP, Acmy, IMT, PFR, IL-6, GM (p <0.0001), TNF-α, UACR reduced NOx (p <0.01). OLM reduced SBP (p <0.001), TNF-α (p <0.05), IL-6, Acmy, IMT, PFR (p <0.0001), GM (p <0.01), UACR (G3) (p <0.05). ROS increased NOx (G6), reduced TNF-α, UACR (G4) (p <0.05), IL-6, Acmy, IMT (G4), PFR (p <0.0001), GM (p <0.001). ROS potentiated the effect of OLM on UACR. OLM and ROS exert beneficial effects on myocardial, vascular, inflammatory and renal remodeling in nitric oxide deficient rats. The pleiotropic effects of ROS were independent of SBP and TC, mediated by its antioxidant properties.