This Article Full Text Full Text (PDF) All Versions of this Article: 46/5/1093    most recent 01.HYP.0000184652.93583.77v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strawn, W. B. Search for Related Content PubMed PubMed Citation Articles by Strawn, W. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB SPIRONOLACTONE Related Collections Pathophysiology Risk Factors Related Article

(Hypertension. 2005;46:1093.)
© 2005 American Heart Association, Inc.

Editorial Commentaries

Eplerenone Antagonizes Atherosclerosis, But What Is the Agonist?

William B. Strawn

From the Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to William B. Strawn, DVM, PhD, Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157. E-mail bstrawn@wfubmc.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A recent analysis of the Framingham Heart Study implicated elevated serum aldosterone as an independent risk factor for the development of cardiovascular disease.¹ Although adrenal-derived aldosterone may prove to be important in this regard, less evident is the source of aldosterone and the mechanism for mineralocorticoid receptor (MR) activation in studies such as the Randomized ALdactone Evaluation Study (RALES)² and the Eplerenone Post-acute myocardial infarction Heart failure Efficacy and Survival Study (EPHESUS),³ where MR blockade exerts obvious cardiovascular benefit but adrenal aldosterone levels are normal. In this issue of Hypertension, the article by Takai et al⁴ documents such a study and thereby adds to the discussion not only of the applicability of MR blockade in cardiovascular disease but also of the mechanisms for MR activation. The authors report that monkeys with diet-induced hypercholesterolemia treated with the selective MR antagonist eplerenone had reduced extent of atherosclerotic lesions in aorta and carotid arteries compared with placebo-treated monkeys. The results extend the beneficial influence of MR blockade to a model with similarities highly relevant to the atherogenic process in humans.

Rajagopalan et al⁵ were the first to demonstrate that local vascular expression of MR might play a role in atherosclerosis. In this study, dietary hypercholesterolemia in rabbits was associated with increased aorta superoxide generation. Eplerenone administration to hypercholesterolemic rabbits normalized superoxide generation, decreased NADH and NADPH oxidase activity to basal levels, and nearly normalized endothelium-dependent vasorelaxation. A study by Keidar et al⁶ showed similar inhibition of atherosclerosis when eplerenone was administered to . . . [Full Text of this Article]

Related Article:

Eplerenone Inhibits Atherosclerosis in Nonhuman Primates

Shinji Takai, Denan Jin, Michiko Muramatsu, Kazuyoshi Kirimura, Hiroshi Sakonjo, and Mizuo Miyazaki
Hypertension 2005 46: 1135-1139. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				D. Armanini, C. Fiore, L. A Calo, S. Takai, and M. Miyazaki Mononuclear Leukocyte Mineralocorticoid Receptors * Response Hypertension, February 1, 2006; 47(2): e4 - e5. [Full Text] [PDF]