Effects of eplerenone and salt intake on left ventricular remodeling after myocardial infarction in rats.
Eplerenone, a selective aldosterone blocker, has been shown to attenuate cardiac fibrosis and decrease cardiovascular events in both experimental and clinical studies. We examined the cardioprotective effect of eplerenone in myocardial infarction (MI) rats receiving different levels of salt in their diet. The MI rats were randomly divided into five groups: Group CL, animals received a low-salt diet (0.015%); Group EpL, a low-salt diet with eplerenone (100 mg/kg/day in food); Group CH, a high-salt diet (0.9%); Group EpH, a high-salt diet with eplerenone; and Group C, a normal salt diet (0.3%). These diets were continued for 4 weeks. Echocardiographic and histomorphological examinations revealed that the administration of eplerenone significantly improved the cardiac function, significantly suppressed compensatory cardiac hypertrophy and significantly reduced cardiac fibrosis in both the interstitial and the perivascular areas in the high-salt diet group (Group EpH). However, eplerenone had no observable effects in the low-salt diet group (Group EpL). Also, these examinations demonstrated that the left ventricular remodeling after MI was suppressed and the cardiac function was improved in the group receiving a low-salt diet without eplerenone (Group CL), even though there was a significant increase of aldosterone level in blood, in comparison to the group receiving a high-salt diet without eplerenone (Group CH). These results indicate that the cardioprotective effect of eplerenone varies depending on the salt intake.
Urabe
Akihiro
A
Division of Cardiology, Department of Internal Medicine, the Jikei University School of Medicine, Tokyo, Japan. a-urabe@jikei.ac.jp
Izumi
Takehiko
T
Abe
Yuichi
Y
Taniguchi
Ikuo
I
Mochizuki
Seibu
S
D000450:Aldosterone / Q000097:blood; D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology; D004039:Diet, Sodium-Restricted; D004452:Echocardiography; D000077545:Eplerenone; D005355:Fibrosis / Q000503:physiopathology; D018565:Food-Drug Interactions; D006321:Heart / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D012965:Sodium Chloride; D000450:Aldosterone; D000077545:Eplerenone