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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.

Abstract
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 angio-tensin-I-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 less than 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.
AuthorsE F Smith 3rd, J W Egan, F R Goodman, M B Zimmerman, R L Webb, L G Ribeiro
JournalPharmacology (Pharmacology) Vol. 37 Issue 4 Pg. 254-63 ( 1988) ISSN: 0031-7012 [Print] Switzerland
PMID2973611 (Publication Type: Journal Article)
Chemical References
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzazepines
  • Creatine Kinase
  • benazeprilat
  • libenzapril
Topics
  • Angiotensin-Converting Enzyme Inhibitors (pharmacology)
  • Animals
  • Benzazepines (pharmacology)
  • Blood Pressure (drug effects)
  • Cardiomegaly (drug therapy)
  • Coronary Disease (drug therapy, physiopathology)
  • Creatine Kinase (metabolism)
  • Male
  • Myocardium (enzymology)
  • Rats
  • Rats, Inbred Strains

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