Role of cardiac aldosterone in ventricular remodeling in rat myocardial infarction

Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently re ported in rat heart. However, regulation of this synthesis in pathophysiolo gical states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Lev els of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Ald o-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoa ssay. MI raised AS mRNA levels by 2.0-fold (p<0.05) but downregulated that of 11 beta H by 2.4 fold (p<0.05) in the noninfarcted part of the left vent ricle (LV). Cardiac steroids production followed a similar pattern of regul ation. Aldo level was increased in MI (319+/-85 vs 87+/-11 pg/mg of protein in control. p<0.05) whereas that of B fell (2.412+/-318 vs 4.624+/-857 pg/ mg of protein in control, p<0.05). MI also induced an 1.9-fold increase in cardiac Ang II level. Such cardiac regulations were prevented by Ang II-AT1 receptor antagonist losartan (8 mg/hg/day) treatment. The Aldo receptor an tagonist spironolactone (20 mg/hg/day) had no effect, Plasma Aldo and B, an d adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatmen t. The MI-induced collagen deposition in noninfarcted area of the LV was re duced by both spironoIactone and losartan treatments by 1.6- and 2.5-fold, respectively These data indicate that MI is associated with tissue-specific activation o f myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldoster one level may be involved in post-MI ventricular remodeling.