CARDIOPROTECTIVE EFFECT OF PROBUCOL IN THE ATHEROSCLEROSIS-PRONE JCR-LA-CP RAT

Probucol is an antihyperlipidemic agent with antioxidant effects and a ntiatherosclerotic properties in hypercholesterolemic conditions. The JCR:LA-corpulent strain of rats exhibits all aspects of the human 'met abolic syndrome' characterized by obesity, insulin resistance, hypertr iglyceridemia, atherogenesis, and ischemic myocardial damage. Male rat s were treated with 100 mg/kg body weight probucol from 6 to 12 weeks or from 6 to 39 weeks of age. Short-term metabolic effects were assess ed at 12 weeks and both metabolic and cardiovascular effects at 39 wee ks of age. Probucol treatment of corpulent male rats did not reduce pl asma lipid concentrations or hyperinsulinemia. The index of severity o f intimal lesions of the aortic arch was not different from that of co ntrols, although the lesions appeared to be qualitatively more severe. There were significantly fewer adherent macrophages on the endothelia l surface. The endothelial layer was unchanged and smoothly covered th e vascular surface, including the intimal lesions. Notwithstanding the extensive atherosclerotic lesions, probucol-treated rats had markedly fewer ischemic myocardial lesions. The cardioprotective effect, possi bly due to the antioxidant properties of probucol, appears to occur at the level of the endothelium and occurs in the presence of continuing obesity, hyperinsulinemia, hypertriglyceridemia, and atherosclerosis. (C) 1998 Elsevier Science B.V. All rights reserved.