Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction.
OBJECTIVE
To examine the effects of eplerenone, a selective aldosterone blocker, on cardiac function after myocardial infarction (MI) and myocardial remodelling related transcriptional factors and mRNA expression in non-infarcted myocardium.


METHODS
MI was induced by ligation of the coronary artery in Wistar rats. Rats were randomly assigned to a vehicle treated group or an eplerenone treated group (100 mg/kg/day).


RESULTS
At four weeks after MI, left ventricular (LV) end diastolic pressure, LV weight, and LV end diastolic dimension were increased in MI rats. Eplerenone significantly reduced the increase in LV end diastolic pressure, LV weight, and LV end diastolic dimension. In the MI rats the decreased ejection fraction indicated systolic dysfunction and the increased E wave to A wave ratio and E deceleration rate indicated diastolic dysfunction. Eplerenone significantly attenuated this systolic and diastolic dysfunction. Myocardial interstitial fibrosis, transcriptional activities of activator protein 1 and nuclear factor kappaB, and mRNA expression of monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, atrial natriuretic peptide, brain natriuretic peptide, and collagen types I and III were significantly increased at four weeks after MI. Eplerenone significantly attenuated interstitial fibrosis and suppressed transcriptional activity and mRNA expression of these genes.


CONCLUSIONS
When administered after MI, eplerenone prevents cardiac remodelling accompanied by systolic and diastolic dysfunction and inhibits abnormal myocardial transcriptional activities and gene expression.
Enomoto
S
S
Department of Internal Medicine and Cardiology, Osaka City University Medical School, Japan.
Yoshiyama
M
M
Omura
T
T
Matsumoto
R
R
Kusuyama
T
T
Kim
S
S
Izumi
Y
Y
Akioka
K
K
Iwao
H
H
Takeuchi
K
K
Yoshikawa
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D003331:Coronary Vessels; D015150:Echocardiography, Doppler; D000077545:Eplerenone; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D008026:Ligation / Q000379:methods; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*; D020257:Ventricular Remodeling / Q000187:drug effects*
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D014157:Transcription Factors; D013148:Spironolactone; D000077545:Eplerenone