Cardiovascular effects of the new angiotensin-converting-enzyme inhibitor, cilazapril, in anesthetized and conscious dogs

J Cardiovasc Pharmacol. 1986 Jan-Feb;8(1):99-108. doi: 10.1097/00005344-198601000-00016.

Abstract

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.

MeSH terms

  • Anesthesia
  • Angiotensin-Converting Enzyme Inhibitors*
  • Animals
  • Antihypertensive Agents
  • Blood Pressure / drug effects
  • Cilazapril
  • Diuresis / drug effects
  • Dogs
  • Enalapril / pharmacology
  • Female
  • Heart Rate / drug effects
  • Hemodynamics / drug effects*
  • Hypertension, Renovascular / drug therapy
  • Hypertension, Renovascular / physiopathology
  • Kidney / drug effects
  • Kidney / physiology
  • Pyridazines / pharmacology*
  • Renin-Angiotensin System / drug effects

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Pyridazines
  • Cilazapril
  • Enalapril