[Role of cardiac aldosterone in post-infarction ventricular remodeling in rats].
Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently reported in rat heart. However, regulation of this synthesis in pathophysiological states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Levels of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Aldo-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoassay. 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 ventricle (LV). Cardiac steroids production followed a similar pattern of regulation. 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/kg/day) treatment. The Aldo receptor antagonist spironolactone (20 mg/kg/day) had no effect. Plasma Aldo and B, and adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatment. The MI-induced collagen deposition in noninfarcted area of the LV was reduced by both spironolactone and losartan treatments by 1.6- and 2.5-fold, respectively. These data indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.
Silvestre
J S
JS
INSERM U127, hôpital Lariboisière, université Denis-Diderot, Paris.
Heymes
C
C
Oubénaïssa
A
A
Robert
V
V
Aupetit-Faisant
B
B
Carayon
A
A
Swynghedauw
B
B
Delcayre
C
C
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D020257:Ventricular Remodeling
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase