Comparative hemodynamic effects of MK-422, a converting enzyme inhibitor, and a renin inhibitor in dogs with acute left ventricular failure.
The angiotensin-converting enzyme (ACE) inhibitor MK-422 (enalaprilat) was compared with the potent renin inhibitor SCRIP for its ability to improve left ventricular function in closed-chest dogs. Acute left ventricular failure (ALVF) was induced by repeated embolization (EMB) of the left coronary arterial vasculature with 50-micron plastic microspheres. Baseline stability data were obtained in 30 dogs in which the evolution of ALVF was monitored over time. Guided by a progressive rise in left ventricular end-diastolic pressure (LVEDP), a stepwise perturbation of the coronary circulation with microspheres over 30 min caused reductions in left ventricular dP/dt and cardiac output, averaging 47 and 40%, respectively. EMB reduced heart rate (20 beats/min) and mean arterial pressure by approximately 20 mm Hg which, along with other hemodynamic variables remained stable after induction of heart failure. MK-422 (100 micrograms/kg i.v.) given 45 min after ALVF was induced, decreased mean arterial pressure by 20 mm Hg (p less than 0.05) and reduced total peripheral resistance (TPR) from 5,453 to 4,150 dyne X s X cm-5 (p less than 0.05). The decline in LVEDP (from 14 +/- 1 to 11 +/- 1 mm Hg) and TPR suggests that MK-422 dilates resistance and, conceivably, capacitance vessels. In dogs with sham EMB (vehicle injections into coronary circulation), MK-422 reduced arterial pressure but had no important effects on the other hemodynamic indices.(ABSTRACT TRUNCATED AT 250 WORDS)
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004151:Dipeptides / Q000494:pharmacology*; D004285:Dogs; D015773:Enalaprilat; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D000092502:Renin Inhibitors
D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine; D004151:Dipeptides; D015773:Enalaprilat; D009842:Oligopeptides; D012083:Renin; D000092502:Renin Inhibitors; C041553:renin inhibitory peptide, statine