Activation of Cardiac Aldosterone Production in Rat Myocardial Infarction: Effect of Angiotensin II Receptor Blockade and Role in Cardiac Fibrosis

Abstract

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 11β-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.