Cardiovascular Effects of the New Angiotensin-Converting-Enzyme Inhibitor, Cilazapril, in Anesthetized and Conscious Dogs

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Abstract
Cilazapril is a new angiotensin-converting enzyme inhibitor. In conscious renal-hypertensive dogs, cilazapril (2 .times. 10 mg/kg/day p.o) caused a long-lasting (> 24 h) decrease in systolic arterial blood pressure, the magnitude of which was potentiated by pretreatment with furosemide. A maximal fall in systolic blood pressure of 39 .+-. 6 mm Hg (from 145 .+-. 5 to 106 .+-. 7 mm Hg) was recorded. The antihypertensive effect did not decline with repeated administration and was accompanied by only a slight increase in heart rate. Cilazapril also reduced systolic blood pressure in furosamide-pretreated normotensive dogs. Hemodynamic studies in anesthetized dogs revealed that cilazapril (0.03-1 mg/kg i.v.) caused a fall in mean arterial and left ventricular systolic pressures. At the highest dose of 1 mg/kg i.v., the blood-pressure-lowering effect (-27%) was due to a decrease in total peripheral resistance (-12%) and cardiac output (-16%). Intravenous administration of cilazapril to anesthetized dogs resulted in a rise in plasma renin activity and a significant fall in plasma angiotensin II levels. In conscious normotensive dogs, cilazapril (0.3-10 mg/kg p.o.) exerted diuretic and saluretic effects, which were accompanied by a significant increase in renal plasma flow (46%), but only a slight rise in the glomerular filtration rate. These results characterize cilazapril as an effective and long-lasting antihypertensive drug, with diuretic activity and, possibly, preload- as well as afterload-reducing properties.