Inhibition of myocardial lesions in the JCR:LA-corpulent rat by captopril.
The JCR:LA-cp rat is a unique strain that, if homozygous for the autosomal recessive cp gene, is obese and exhibits the metabolic syndrome of insulin resistance, hyperinsulinemia, and hypertriglyceridemia. Obese male rats spontaneously develop advanced atherosclerosis and ischemic myocardial lesions. The angiotensin-converting enzyme inhibitor, captopril, was administered to obese rats at 30 mg/kg body weight from 6 to 39 weeks of age. There were no significant changes in food consumption or body weights of the treated animals. Insulin sensitivity was not improved. Plasma insulin levels were unaltered, but the volume density of the islets of Langerhans was halved, reflecting both reduced hyperplasia and a more normal islet structure. Triglyceride concentrations were not reduced, but unesterified cholesterol and cholesteryl esters decreased by 50% and 34%, respectively (p < 0.01). The impaired nitric oxide-mediated vascular relaxation of the obese rats was not improved, and the relaxant sensitivity to acetylcholine as indicated by the median effective concentration (EC50) was reduced. In vitro, captopril significantly reduced the basal tension of aortic rings from untreated rats, antagonized the contractile effects of norepinephrine, and induced complete relaxation of the contraction in response to 10(-7) M norepinephrine. The severity of spontaneous, raised atherosclerotic lesions of the aortic arch at age 39 weeks was not significantly decreased by captopril treatment. In contrast, the frequency of ischemic myocardial lesions was reduced by 78% (p < 0.01). The protective effects of captopril on the heart and pancreas in this animal model of type II diabetes and atherosclerosis are probably the result of its bradykinin-enhancing effects.
Russell
J C
JC
Department of Surgery, University of Alberta, Edmonton, Canada.
Graham
S E
SE
Amy
R M
RM
Dolphin
P J
PJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D002216:Captopril / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D009765:Obesity / Q000150:complications*; D051381:Rats; D011922:Rats, Mutant Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril