Effects of two angiotensin converting enzyme inhibitors and hydralazine on coronary circulation in hypertensive rats.
The goal of the present study was to compare the effects of cilazapril, a new long-acting angiotensin converting enzyme inhibitor, to those of captopril and hydralazine on the coronary vascular bed. For this purpose, spontaneously hypertensive rats were treated for 4 months with either placebo, 10 mg/kg/day cilazapril, 100 mg/kg/day captopril, or 10 mg/kg/day hydralazine. At the end of treatment, maximal coronary blood flow was measured during maximal coronary vasodilation with adenosine in isolated perfused hearts. Cilazapril was the most effective drug in increasing maximal coronary blood flow. Captopril was less effective in improving maximal coronary blood flow but was as effective as cilazapril in reducing cardiac hypertrophy. Hydralazine had an extremely small effect on cardiac hypertrophy and maximal coronary flow reserve. The ranking of efficacy was similar for the reduction of vessel wall hypertrophy in the coronary arteries and arterioles. Because of the higher efficacy of cilazapril compared with captopril, a second experiment was performed in which 10 mg/kg/day cilazapril was compared with 100 mg/kg/day captopril and 300 mg/kg/day captopril after 1 month of treatment. Captopril increased maximal coronary flow and decreased cardiac hypertrophy to the same level as cilazapril only at the highest dose. We conclude that angiotensin converting enzyme inhibitors, in contrast to hydralazine, can increase markedly maximal coronary flow in spontaneously hypertensive rats but that this increase does not always parallel the decrease of cardiac hypertrophy and is closely dose dependent.
Clozel
J P
JP
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Véniant
M
M
Hess
P
P
Sprecher
U
U
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000517:prevention & control; D017315:Cilazapril; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D010477:Perfusion; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D011724:Pyridazines; D017315:Cilazapril; D006830:Hydralazine; D002216:Captopril