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Medline ® Abstract for Reference 3

of 'Actions of angiotensin II on the heart'

Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.
Silvestre JS, Heymes C, Oubénaïssa A, Robert V, Aupetit-Faisant B, Carayon A, Swynghedauw B, Delcayre C
Circulation. 1999;99(20):2694.
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 x kg-1 x d-1), losartan- (8 mg x kg-1 x d-1), spironolactone plus losartan-, and L-NAME- (5 mg x kg-1 x 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 11beta-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 AT1-subtype receptor and may be involved in post-MI ventricular fibrosis and in control of tissue norepinephrine concentration.
INSERM U127, IFR Circulation, UniversitéD. Diderot, Paris, France.