Rosuvastatin, a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Decreases Cardiac Oxidative Stress and Remodeling in Ren2 Transgenic Rats

• DOI: 10.1210/en.2006-1355
• Publication Date: 2007-02-23T12:14:34Z
• Authors: Javad Habibi; Adam Whaley-Connell; Mahnaz A. Qazi; Melvin R. Hayden; Shawna A. Cooper; Anthony Tramontano; John Thyfault; Craig Stump; Carlos Ferrario; Ranganath Muniyappa; James R. Sowers
• Keywords: Nitrotyrosine; Apocynin; Malondialdehyde

Angiotensin-II (Ang-II)-stimulated increases in nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase activity and oxidative stress are known to play a key role cardiac remodeling. Inhibition of isoprenylation activation small G proteins, such as Rac1, component NADPH oxidase, may mediate the antioxidant actions 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). In this study, we investigated effects rosuvastatin on remodeling transgenic rats (Ren2) overexpressing mouse renin gene with elevated levels Ang-II. We treated 6- 7-wk-old Ren2 age-matched Sprague-Dawley (SD) (10 mg/kg.d) or vehicle for 3 wk. At end treatment period, left ventricular mass, wall thickness, ejection fraction (by echocardiography), light microscopy immunohistochemistry) were assessed. addition, myocardial content nitrotyrosine, malondialdehyde, NADPH-oxidase subunits (gp91(phox), p40(phox), p22(phox)), Rac1 analyzed by immunochemistry. Systolic blood pressure was significantly higher rats, compared SD (P < 0.05); had no significant effect systolic either group. Ren2, but not improved fraction, hypertrophy, perivascular fibrosis 0.05). administration decreased accentuated gp91(phox), p22(phox), expression. These changes accompanied parallel reduction lipid peroxidation (nitrotyrosine malondialdehyde content) results suggest that vivo statin through its direct heart reduces including mass regression Ang-II-dependent model.