Anti-shock actions of a new converting enzyme inhibitor, enalaprilic acid, in hemorrhagic shock in cats

J. G. Freeman, C. E. Hock, J. S. Edmonds, A. M. Lefer

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13 Scopus citations

Abstract

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 < .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 < .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 < .01) and myocardial depressant factor activities (P < .01), and plasma amino-nitrogen concentrations (P < .05) observed in the untreated hemorrhaged cats. These results indicate that enalaprilic acid improved the hemodynamic and metabolic status of cats in hemorrhagic shock.

Original languageEnglish (US)
Pages (from-to)610-615
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume231
Issue number3
StatePublished - 1984
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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