Spironolactone prevents cardiac collagen proliferation after myocardial infarction in rats.
1. Aldosterone has been considered a key hormone in the regulation of water, sodium and potassium metabolism, thus influencing blood pressure regulation. More recently, several studies have demonstrated that aldosterone is also produced in extra-adrenal tissues (e.g. the heart), suggesting a paracrine effect for aldosterone, such as to increase collagen synthesis in the heart. 2. Because aldosterone production in the heart increases after myocardial infarction (MI), we investigated the effect of chronic administration of spironolactone, an aldosterone receptor antagonist, in rats after MI compared with the effects produced by losartan and hydralazine. 3. Myocardial infarction was produced in male Wistar rats by surgical ligature of the left coronary artery. Sham-operated animals were used as controls. 4. Spironolactone (20 mg/kg per day), losartan (15 mg/kg per day) or hydralazine (20 microg/kg per day) were administered after MI and used for 1 month. 5. At the end of the treatment period, animals underwent haemodynamic recording (arterial and intraventricular pressures). The collagen content of the heart was evaluated by measuring the hydroxyproline (OH-Pro) concentration in right (RV) and left ventricle (LV) muscle fragments. 6. Infarct size was unaffected by drug treatments. The increased LV end-diastolic pressure observed in MI rats was prevented by losartan and remained unchanged following administration of spironolactone or hydralazine. 7. Losartan prevented RV and LV hypertrophy, as well as collagen proliferation in both ventricles, after MI. The postinfarction hypertrophy observed in RV and LV after MI remained unchanged in infarcted groups treated with spironolactone or hydralazine. 8. The OH-Pro concentration was significantly reduced in LV muscle in the MI group treated with spironolactone (682 +/- 40 vs 557 +/- 21 microg/g for MI vs MI + spironolactone, respectively; P < 0.05), an effect not observed in the hydralazine-treated group. 9. These data suggest that spironolactone prevents collagen proliferation in the surviving myocardium by mechanisms independent of the loading conditions of the heart chambers. Control of postinfarction hypertrophy and collagen accumulation produced by losartan seems to depend on the reduction in loading conditions of the heart chambers.
D000818:Animals; D002921:Cicatrix / Q000378:metabolism; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006830:Hydralazine / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*
D006830:Hydralazine; D013148:Spironolactone; D003094:Collagen; D019808:Losartan