Potassium canrenoate, an aldosterone receptor antagonist, reduces isoprenaline-induced cardiac fibrosis in the rat.
The purpose of the present study was to determine whether the administration of an antagonist of aldosterone could prevent the fibrosis induced by an acute injection of isoprenaline. Male Wistar rats were submitted to one subcutaneous injection of isoprenaline (400 mg/kg) and were simultaneously treated with potassium canrenoate in drinking water (20 mg/kg/day) started 5 days before the injection of isoprenaline. Two months later, echocardiographic and hemodynamic measurements were performed. Then, the heart was prepared for morphometric histology and quantification of fibrosis in the left ventricle. Heart and left ventricular weights were increased significantly by isoprenaline. Potassium canrenoate attenuated this increase. The administration of isoprenaline increased significantly end diastolic diameter and end systolic volume compared with control. These changes were increased further with the addition of potassium canrenoate. In contrast, the fibrosis induced by isoprenaline was reduced significantly by potassium canrenoate at the three section levels. Potassium canrenoate attenuated the fibrosis but not the enhanced dilatation of the left ventricle induced by isoprenaline.
Bos
Romain
R
Service de Pharmacologie, CHU Pitié Salpêtrière, 47 boulevard de l'Hôpital, 75651 Paris cedex 13, France.
Mougenot
Nathalie
N
Médiani
Odile
O
Vanhoutte
Paul M
PM
Lechat
Philippe
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002191:Canrenoic Acid / Q000627:therapeutic use*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D018377:Neurotransmitter Agents / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D000451:Mineralocorticoid Receptor Antagonists; D018377:Neurotransmitter Agents; D002191:Canrenoic Acid; D007545:Isoproterenol