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ADDITIVE BENEFICIAL EFFECTS OF AMLODIPINE AND ATORVASTATIN IN REVERSING ADVANCED CARDIAC HYPERTROPHY IN ELDERLY SPONTANEOUSLY HYPERTENSIVE RATS.

Author(s): Lu JC, Cui W, Zhang HL, Liu F, Han M, Liu DM, Ying HN, Zhang K, Du J

Affiliation(s): Department of Cardiology, Second Hospital of Hebei Medical University, Shijiazhuang Hebei, China;

Publication date & source: 2009-04-27, Clin Exp Pharmacol Physiol., [Epub ahead of print]

1. Additive beneficial effects of amlodipine and atorvastatin on cardiovascular disease have been reported. However, it is still unclear whether combination of amlodipine and atorvastatin has additive effects on regression of advanced cardiac hypertrophy in hypertension. We examined their effects on advanced cardiac hypertrophy in elderly spontaneously hypertensive rats (SHR). 2. Thirty-six-week-old rats were randomly allocated into four groups of 12: vehicle-treated control SHR, amlodipine-treated SHR (10 mg/kg/day), atorvastatin-treated SHR (10 mg/kg/day), amlodipine/atorvastatin-treated SHR (both 10 mg/kg/day). Drugs were administered by oral gavage every morning over 12 weeks before hearts were harvested for analysis. 3. Co-administration of amlodipine and atorvastatin significantly suppressed cardiomyocyte hypertrophy, interstitial fibrosis and upregulation of hypertrophic and profibrotic genes, and improved left ventricular diastolic dysfunction, to a greater extent than amlodipine monotherapy. Further beneficial effects of combination therapy on advanced cardiac hypertrophy were associated with a greater reduction of NADPH-oxidase-mediated cardiac reactive oxygen species (ROS), rather than decreased blood pressure and serum cholesterol level. To elucidate the underlying molecular mechanism, we examined cardiovascular NADPH oxidase subunits. We found that amlodipine clearly attenuated the expression of p47(phox) and p40(phox), and slightly reduced p22(phox) and Rac-1 level in heart tissue. Combined amlodipine and atorvastatin led to a further reduction in p22(phox), p47(phox) and Rac-1 protein levels compared with amlodipine alone. 4. Combined amlodipine and atorvastatin treatment had a greater beneficial effect on advanced cardiac hypertrophy in contrast to amlodipine monotherapy. The benefits were likely related with additive suppression of NADPH oxidase-mediated ROS generation.

Page last updated: 2009-10-20

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