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Effects of Two Nonsulfhydryl Angiotensin-Converting Enzyme Inhibitors, CGS 14831 and CGS 16617, on Myocardial Damage and Left-Ventricular Hypertrophy following Coronary Artery Occlusion in the Rat

1988; Karger Publishers; Volume: 37; Issue: 4 Linguagem: Inglês

10.1159/000138474

1423-0313

Edward F. Smith, J. Egan, Frank R. Goodman, M. B. Zimmerman, Randy L. Webb, Lair G.T. Ribeiro,

Renin-Angiotensin System Studies

The present study was designed to examine the effects of two new angiotensin-converting enzyme (ACE) inhibitors, CGS 14831 and CGS 16617 (3 mg/kg i.v. 1 min prior to occlusion and 4 and 24 h after occlusion), on myocardial ischemic (MI) damage and left-ventricular hypertrophy in rats. Administration of CGS 14831 or CGS 16617 inhibited angiotensin-1-induced pressor responses by 40–100% for 4 h after each dose. Myocardial creatine phosphokinase (CK) levels were 10.6 ± 0.6 U/mg protein in sham-MI animals, and following coronary artery occlusion for 48 h were decreased to 4.1 ± 0.2 U/mg protein in MI + vehicle animals (p < 0.01). CGS 14831 and CGS 16617 attenuated the decrease in CK content and resulted in 47 and 40% sparing, respectively, of the left-ventricular free wall. Neither agent attenuated the left-ventricular hypertrophy which developed following coronary artery occlusion. These data indicate that the nonsulfhydryl ACE inhibitors CGS 14831 and CGS 16617 have a significant cardioprotective effect in rats surviving 48 h, and suggest a potential therapeutic usefulness of these agents for the treatment of ischemia-induced heart failure.