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.
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.
Smith
E F
EF
Research Department, Ciba-Geigy Corp., Summit, N.J.
Egan
J W
JW
Goodman
F R
FR
Zimmerman
M B
MB
Webb
R L
RL
Ribeiro
L G
LG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D003402:Creatine Kinase; C052133:benazeprilat; C052134:libenzapril