Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice

Journal of Cardiovascular Pharmacology
Shlomo KeidarMichael Aviram

Abstract

Oxidative stress is involved in the pathogenesis of atherosclerosis, and angiotensin II (AT-II) induces oxidative stress and enhances atherogenesis. Aldosterone, which has an important role in the pathology of heart failure, has recently been implicated as a mediator of AT-II biologic activities. In this study, we analyzed whether administration of the selective aldosterone blocker eplerenone to atherosclerotic apolipoprotein E-deficient (E0) mice would affect their oxidative status and atherogenesis. Apolipoprotein E-deficient mice were administered chow containing eplerenone (200 mg/kg/day) for 3 months. Blood pressure, serum and macrophage oxidative status, and aortic atherosclerotic lesion area were evaluated in mice treated with eplerenone compared with untreated mice. Eplerenone administration significantly decreased systolic and diastolic blood pressure by 12% and 11%, respectively, compared with untreated mice. Serum susceptibility to lipid peroxidation decreased by as much as 26%, and serum paraoxonase activity increased by 28% in eplerenone-treated mice compared with untreated mice. Peritoneal macrophages from eplerenone-treated mice contained reduced levels of lipid peroxides, and their macrophage oxidation of low-de...Continue Reading

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