Cardiovascular effects of the new angiotensin-converting-enzyme inhibitor, cilazapril, in anesthetized and conscious dogs.
Cilazapril is a new angiotensin-converting-enzyme inhibitor. In conscious renal-hypertensive dogs, cilazapril (2 X 10 mg/kg/day p.o.) caused a long-lasting (greater than 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 furosemide-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.
M
M
Holck
W
W
Fischli
F
F
Hefti
M
M
Gerold
D000758:Anesthesia; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D017315:Cilazapril; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D011724:Pyridazines; D017315:Cilazapril; D004656:Enalapril