Published Online
on October 3, 2005

A more recent version of this article appeared on November 1, 2005

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Submitted on June 3, 2005
Revised on June 23, 2005

Eplerenone Inhibits Atherosclerosis in Nonhuman Primates

Shinji Takai^*; Denan Jin; Michiko Muramatsu; Kazuyoshi Kirimura; Hiroshi Sakonjo; and Mizuo Miyazaki

From the Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan (S.T., D.J., M.M., M.M.); and Environmental Biological Life Science (BILIS) Research Center, Koka City, Shiga Japan (K.K., H.S.).

^* To whom correspondence should be addressed. E-mail: pha010{at}art.osaka-med.ac.jp.

Abstract--Aldosterone may be involved in the pathogenesis of atherosclerosis. We investigated the effect of eplerenone, a selective mineralocorticoid receptor blocker, on atherosclerosis in monkeys fed a high-cholesterol diet. Monkeys fed a high-cholesterol diet for 9 months were divided into 3 groups: those treated with a low dose of eplerenone (30 mg/kg per day); those treated with a high dose of eplerenone (60 mg/kg per day); and the placebo-treated group. The normal group consisted of monkeys fed a normal diet. There were no significant differences in blood pressure and cholesterol levels between the placebo- and eplerenone-treated groups. On the other hand, monocyte chemoattractant protein-1 and malondialdehyde-modified LDL were significantly higher in the placebo-treated group than in the normal group, whereas they were suppressed in the eplerenone-treated groups. The ratio of intimal volume to total volume by intravascular ultrasound analysis imaging of the aortas was dose-dependently lower in the eplerenone-treated groups than in the placebo-treated group. Acetylcholine-induced vasorelaxation was significantly weaker in the placebo-treated group than in the normal group, but the vasorelaxation was strengthened in the eplerenone-treated groups. A significant upregulation of angiotensin-converting enzyme activity was observed in the placebo-treated group, but the activity was suppressed in the eplerenone-treated groups. In conclusion, eplerenone may strengthen the endothelium-dependent relaxation and suppress angiotensin-converting enzyme activity in the vasculature, thus preventing the development of atherosclerosis in nonhuman primates.

Key words: aldosterone • angiotensin • atherosclerosis • endothelium • hypercholesterolemia

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Eplerenone Antagonizes Atherosclerosis, But What Is the Agonist?

William B. Strawn
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