Anti-shock actions of a new converting enzyme inhibitor, enalaprilic acid, in hemorrhagic shock in cats.
A new angiotensin converting enzyme inhibitor, enalaprilic acid (MK-422), was given in a bolus of 0.5 mg/kg i.v., followed by an infusion of 0.25 mg/kg/hr to determine its effects in hemorrhagic shock. MK-422 produced no significant hemodynamic effects in sham shock controls, yet it effectively blocked the pressor effect of exogenously administered angiotensin I throughout the 260-min experimental period and reduced angiotensin converting enzyme activity by 90% as determined by radiochemical assay. In vitro studies on cat papillary muscles and pancreatic homogenates revealed no direct inotropic or antiproteolytic effect of enalaprilic acid. Nevertheless, converting enzyme inhibitor treatment maintained postreinfusion mean arterial blood pressure at a significantly higher value (P less than .01) than that of untreated hemorrhaged animals (66 +/- 5 vs. 27 +/- 10 mm Hg, respectively). Superior mesenteric artery flow for hemorrhaged cats was significantly higher (P less than .05) in the treated group both during the end of the oligemic period (6.1 +/- 0.4 vs. 3.8 +/- 0.8 ml/kg/min) and during the postreinfusion period (6.5 +/- 0.7 vs. 1.9 +/- 1.0 ml/kg/min). Moreover, enalaprilic acid blunted the marked rise in plasma cathepsin D (P less than .01) and myocardial depressant factor activities (P less than .01), and plasma amino-nitrogen concentrations (P less than .05) observed in the untreated hemorrhaged cats. These results indicate that enalaprilic acid improved the hemodynamic and metabolic status of cats in hemorrhagic shock.
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002402:Cathepsin D / Q000097:blood; D002415:Cats; D004151:Dipeptides / Q000494:pharmacology*; D015773:Enalaprilat; D008297:Male; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D000803:Angiotensin I; D002402:Cathepsin D; D015773:Enalaprilat