Document Detail

Activation of cardiac aldosterone production in rat myocardial infarction: effect of angiotensin II receptor blockade and role in cardiac fibrosis.
MedLine Citation:
PMID:  10338465     Owner:  NLM     Status:  MEDLINE    
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.
J S Silvestre; C Heymes; A Oubénaïssa; V Robert; B Aupetit-Faisant; A Carayon; B Swynghedauw; C Delcayre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  99     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-06-15     Completed Date:  1999-06-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2694-701     Citation Subset:  AIM; IM    
INSERM U127, IFR Circulation, Université D. Diderot, Paris, France.
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MeSH Terms
Aldosterone / biosynthesis*
Angiotensin II / metabolism
Atrial Natriuretic Factor / genetics
Cardiomegaly / pathology
Gene Expression
Heart / physiopathology
Heart Ventricles
Myocardial Infarction / metabolism*,  pathology*
Myocardium / metabolism*,  pathology*
Norepinephrine / metabolism
Rats, Wistar
Receptors, Angiotensin / antagonists & inhibitors*
Steroids / biosynthesis
Reg. No./Substance:
0/Receptors, Angiotensin; 0/Steroids; 11128-99-7/Angiotensin II; 51-41-2/Norepinephrine; 52-39-1/Aldosterone; 85637-73-6/Atrial Natriuretic Factor

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