Cardioprotective effect of probucol in the atherosclerosis-prone JCR:LA-cp rat

Abstract

Probucol is an antihyperlipidemic agent with antioxidant effects and antiatherosclerotic properties in hypercholesterolemic conditions. The JCR:LA-corpulent strain of rats exhibits all aspects of the human 'metabolic syndrome' characterized by obesity, insulin resistance, hypertriglyceridemia, atherogenesis, and ischemic myocardial damage. Male rats 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 assessed at 12 weeks and both metabolic and cardiovascular effects at 39 weeks of age. Probucol treatment of corpulent male rats did not reduce plasma lipid concentrations or hyperinsulinemia. The index of severity of intimal lesions of the aortic arch was not different from that of controls, although the lesions appeared to be qualitatively more severe. There were significantly fewer adherent macrophages on the endothelial surface. The endothelial layer was unchanged and smoothly covered the vascular surface, including the intimal lesions. Notwithstanding the extensive atherosclerotic lesions, probucol-treated rats had markedly fewer ischemic myocardial lesions. The cardioprotective effect, possibly 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.