Cardioprotective effects of enalapril in acute myocardial ischemia.
Enalapril, a new potent orally active angiotensin-converting enzyme inhibitor, was studied in cats subjected to acute myocardial ischemia. Enalapril, administered intravenously (2 mg/kg, plus 2 mg/kg/h) 30 min after ligation of the left coronary artery, significantly reduced the pressure-rate index, an indicator of myocardial oxygen demand. This was confirmed in isolated cat papillary muscles where enalapril reduced contractile force by 5-10%. During myocardial ischemia, enalapril reversed the elevated S-T segment of the electrocardiogram toward normal 2 h after the onset of ischemia. Moreover, enalapril significantly blunted the increases in circulating creatine kinase (CK) activity, as well as significantly prevented the loss in myocardial CK activity. These changes correlated with reduced myocardial loss of compounds containing free amino-nitrogen. Enalapril effectively acted as a converting enzyme inhibitor over the 5-hour course of the observation period. However, enalapril also acted as an angiotensin antagonist in isolated coronary arteries, a finding that may help explain its efficacy in myocardial ischemia. Enalapril did not appear to stabilize the membranes of cat liver lysosomes, and thus probably does not protect the ischemic myocardium by lysosomal stabilization.
D000208:Acute Disease; D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D003402:Creatine Kinase / Q000378:metabolism; D004151:Dipeptides / Q000627:therapeutic use*; D004562:Electrocardiography; D004656:Enalapril; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010210:Papillary Muscles / Q000187:drug effects; D013722:Teprotide
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; D004656:Enalapril; D000803:Angiotensin I; D013722:Teprotide; D003402:Creatine Kinase