Atherosclerosis

Abstract

Cholesterol-induced rabbit atherosclerosis was inhibited by the antihistaminic, chlorpheniramine, given orally at a rate of either 2, 4, or 8 mg./day/rabbit. Two attempts, both unsuccessful, were made to demonstrate directly the expected chlorpheniramine-mediated decrease in the permeability of the rabbit aortic wall to serum constituents: (1) study of sudan-red-stained frozen sections of aortas from rabbits fed a high-cholesterol diet for a few days, with and without added chlorpheniramine, and (2) a study of the effect of chlorpheniramine on the permeability of the inner aspect of the aorta to I 13l -labeled serum albumin. A possible mechanism, based on aortic reaction to injury, is presented to account for the localization and development of atherosclerosis. This hypothesis led to the selection of chlorpheniramine for study as a possible atherosclerosis-inhibiting agent and underlies the belief that the atherosclerosis-inhibiting effect of this compound is due to inhibition of aortic reaction to injury.