Activation of cardiac aldosterone production in rat myocardial infarction -: Effect of angiotensin II receptor blockade and role in cardiac fibrosis

Background-This study analyzed the regulation and the role of the cardiac steroidogenic system in myocardial infarction (MI). Methods and Results-Seven days after MI, rats were randomized to untreated infarcted group or spironolactone- (20 and 80 mg.kg(-1).d(-1)), losartan-(8 mg.kg(-1).d(-1)), spironolactone plus losartan-, and L-NAME- (5 mg.kg(-1).d(-1)) treated infarcted groups for 25 days. Sham-operated rats served as controls. In the noninfarcted myocardium of the left ventricle (LV). MI raised aldosterone synthase mRNA (the terminal enzyme of aldosterone synthesis) by 2.0-fold and the aldosterone level by 3.7-fold, Conversely, MI decreased 11 beta-hydroxylase mRNA (the terminal enzyme of corticosterone synthesis) by 2.4-fold and the corticosterone level by 1.9-fold. MI also induced a 1.9-fold increase in cardiac angiotensin II level. Such cardiac regulations were completely prevented by treatment of the infarcted heart with losartan. The MI-induced collagen deposition in noninfarcted LV myocardium was prevented by 1.6-fold by both low and high doses of spironolactone and by 2.5-fold by losartan. In addition, norepinephrine level was unchanged in infarcted heart but was attenuated by both losartan and spironolactone treatments. Conclusions-MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This increase is mediated primarily by cardiac angiotensin II via AT(1)-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration.