Effect of a selective aldosterone receptor antagonist in myocardial infarction.
Myocardial infarction (MI) initiates adaptive tissue remodeling, which is essential for heart function (such as infarct healing) but is also important for maladaptive remodeling (for example, reactive fibrosis and left ventricular dilation). The effect of aldosterone receptor antagonism on these processes was evaluated in Sprague-Dawley rats using eplerenone, a selective aldosterone receptor antagonist. Infarct healing and left ventricular remodeling were evaluated at 3, 7, and 28 days after MI by determination of the diastolic pressure-volume relationship of the left ventricle, the infarct-thinning ratio, and the collagen-volume fraction. Eplerenone did not affect reparative collagen deposition as was evidenced by a similar collagen volume fraction in the infarcted myocardium between eplerenone and vehicle-treated groups at 7 and 28 days post-MI. In addition, the thinning ratio, which is an index of infarct expansion, was comparable between the eplerenone and vehicle-treated animals at 7 and 28 days post-MI. A protective effect of eplerenone was demonstrated at 28 days post-MI, where reactive fibrosis in the viable myocardium was reduced in eplerenone-treated animals compared with vehicle-treated animals. Thus aldosterone receptor antagonism does not retard infarct healing but rather protects against maladaptive responses after MI.
Delyani
J A
JA
Cardiovascular and Metabolic Diseases, Pharmacia Corporation, St. Louis, Missouri 63141, USA. john.a.delyani@pharmacia.com
Robinson
E L
EL
Rudolph
A E
AE
D000818:Animals; D000077545:Eplerenone; D005355:Fibrosis / Q000188:drug therapy; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000502:physiology*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D020257:Ventricular Remodeling
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone