Effects of Eplerenone, a Selective Aldosterone Blocker, on the Progression of Left Ventricular Dysfunction and Remodeling in Rats with Dilated Cardiomyopathy

Abstract

Aldosterone blockade reduces morbidity and mortality in patients with heart failure. We studied the effects of eplerenone, a novel aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after immunization, the surviving Lewis rats were randomized to 1 month’s oral treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in group L died during the course of treatment. High-dose eplerenone significantly reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight ratio. Eplerenone improved left ventricular function in a dose-dependent manner. Central venous pressure and left ventricular end-diastolic pressure were lower, and ±dP/dt and fractional shortening were higher in group H than group V. Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA expressions of TGF-β₁ and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.