Effects of aldosterone receptor antagonist and angiotensin II type I receptor blocker on cardiac transcriptional factors and mRNA expression in rats with myocardial infarction.

BACKGROUND: Because the effects of an aldosterone receptor antagonist on transcriptional factors and mRNA expression have not been fully examined in myocardial infarction (MI), the present study examined the effects of spironolactone (SPIRO) and candesartan cilexitil (CAN) on activation of activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB) and mRNA expression in the non-ischemic myocardium after MI.

METHODS AND RESULTS: MI was induced by ligation of the coronary artery in Wistar rats, which were separated into (1) vehicle-treated group, (2) CAN-treated group (10 mg/kg per day), (3) SPIRO-treated group (100 mg/kg per day) and (4) CAN + SPIRO-treated group. The activity of both AP-1 and NF-kappaB was significantly increased at 4 weeks after MI. CAN or SPIRO significantly prevented the cardiac remodeling and activity of AP-1 and NF-kappaB. Furthermore, CAN + SPIRO prevented the cardiac remodeling and activation of AP-1 and NF-kappaB, compared with CAN or SPIRO alone. Myocardial atrial natriuretic peptide, brain natriuretic peptide, collagen I and III mRNAs were enhanced by MI, and CAN or SPIRO alone significantly reduced the mRNAs. CAN + SPIRO significantly prevented these mRNAs, compared with CAN or SPIRO alone.

CONCLUSIONS: Both aldosterone and angiotensin II are involved in the myocardial transcriptional activation of AP-1, NF-kappaB and the cardiac remodeling-related mRNAs. The combination of CAN and SPIRO may be a potent therapeutic strategy for preventing cardiac remodeling after MI.