Effects of propranolol on atherogenesis in the cholesterol-fed rabbit.

Abstract

These studies have examined the effects of dl-propranolol, d-propranolol, and metoprolol on aortic atherogenesis in the cholesterol-fed rabbit and have correlated the vascular effects of the drugs with their influence on blood pressure, plasma lipids and lipoproteins, arterial metabolism, and arterial permeability. dl-Propranolol, and, to a lesser extent, d-propranolol, used in clinically relevant doses of 5 mg/kg body weight per day, inhibited the development of aortic atherosclerosis in association with significant reductions in aortic free and esterified cholesterol content. No significant effects of the drugs on blood pressure or on the total amounts or types of circulating lipoproteins were apparent. Accumulation of cholesterol in the liver and adrenal gland was not influenced by propranolol. Aortic acyl CoA:cholesterol acyltransferase and lysosomal enzyme activities were reduced by propranolol administration, but the inhibition may have been secondary to the lesser degrees of atherosclerosis and cholesterol accumulation present. In vitro inhibition of acyl CoA:cholesterol acyltransferase activity by either dl- or d-propranolol was also observed, but occurred only at propranolol concentrations of 10(-3) M or greater. Treatment with dl-propranolol had no significant effect on the rate of transport of labeled albumin across the isolated carotid artery of cholesterol-fed rabbits. Metoprolol administration (6.25 mg/kg body weight per day) had no significant influence on atherogenesis or arterial metabolism in this model. The results suggest that propranolol inhibits in part the development of atherosclerosis in the cholesterol-fed rabbit, and that the effect may be related to a direct action on the arterial wall.