imidapril and Endomyocardial-Fibrosis

It has been widely assumed that the cardiac angiotensin-generating system plays an important role in the development and maintenance of cardiac remodeling caused by pressure overload. The roles of angiotensin-converting enzyme (ACE) in pressure overload-induced cardiac hypertrophy and fibrosis in rats were investigated. Pressure overload was achieved by constricting the abdominal aorta above the renal arteries. After they underwent surgery, the rats were treated with a low or high dose of the ACE inhibitor imidapril (0.07 and 0.7 mg/kg/d s.c.) with an osmotic pump for 4 weeks. High-dose imidapril prevented the increase in blood pressure, cardiac hypertrophy, and fibrosis. Low-dose imidapril inhibited only cardiac fibrosis. ACE activity in the myocardium, but not in serum, was significantly increased in the rats with the banded aorta, and ACE immunoreactivity was increased in the areas of fibrosis. These changes were markedly reduced by both doses of imidapril. These results suggest that the increased local ACE expression contributes to the development of pressure overload-induced cardiac fibrosis but is not responsible for hypertrophy in rats.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cardiomegaly; Collagen Type I; Constriction, Pathologic; Dose-Response Relationship, Drug; Endomyocardial Fibrosis; Imidazoles; Imidazolidines; Male; Myocardium; Peptidyl-Dipeptidase A; Rats; Rats, Sprague-Dawley; Tissue Distribution; Transforming Growth Factor beta; Transforming Growth Factor beta1