Effects of eplerenone, a selective aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy.
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-beta(1) and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.
Wahed
Mir Imam Ibne
MI
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata-shi, Japan.
Watanabe
Kenichi
K
Ma
Meilei
M
Yamaguchi
Kenichi
K
Takahashi
Toshihiro
T
Tachikawa
Hitoshi
H
Kodama
Makoto
M
Aizawa
Yushifusa
Y
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications; D002311:Cardiomyopathy, Dilated / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D000077545:Eplerenone; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D009205:Myocarditis / Q000150:complications; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects*
D024061:Collagen Type III; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D013148:Spironolactone; D000077545:Eplerenone