Hemodynamic effects of angiotensin and renin inhibition in dogs with acute left ventricular failure.
The effects of enalaprilat (MK-422), an angiotensin converting enzyme inhibitor, were compared to those of SCRIP, a renin inhibitor, in experimentally induced left ventricular failure. In anesthetized dogs, acute left ventricular failure was induced by repeated embolization, via the left main coronary artery, with 50 microns plastic microspheres. Embolization significantly increased left ventricular enddiastolic pressure from 6 +/- 1 to 14 +/- 1 (p less than 0.05) mm Hg and decreased both left ventricular maximal dP/dt (3,135 +/- 338 to 1,636 +/- 126 mm Hg/second, p less than 0.05) and cardiac output (3.0 +/- 0.3 to 1.6 +/- 0.1 liters per minute, p less than 0.05). Embolization also significantly reduced heart rate and mean arterial pressure. These parameters remained stable after induction of heart failure. Forty-five minutes after embolization, 16 dogs received enalaprilat (100 microns/kg intravenously) and six dogs received SCRIP (100 microns/kg intravenously followed by 10 microns/kg per minute). Both agents caused similar reductions in left ventricular end-diastolic pressure (21 percent versus 26 percent) and total peripheral resistance (25 percent versus 32 percent) and rise in peak positive cardiac contractility, as measured by (dP/dt)/P, (12 percent versus 11 percent). The data suggest that inhibition of angiotensin II formation by two agents, each or which acts at a different point in the cascade, results in similar beneficial hemodynamic effects in dogs with acute left ventricular failure. In addition, angiotensin converting enzyme inhibition failed to further increase sodium excretion and glomerular filtration rate caused by embolization. In summary, inhibition of angiotensin II production by two different inhibitors of the renin system causes an improvement in left ventricular performance in a model of acute experimental left ventricular failure.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004151:Dipeptides / Q000627:therapeutic use*; D004285:Dogs; D004617:Embolism; D015773:Enalaprilat; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; C041553:renin inhibitory peptide, statine; D015773:Enalaprilat