Hyperalphalipoproteinaemic activity of BRL 26314--II. Inhibition of atherosclerosis in rabbits.

Abstract Optimization of a combination of balloon catheter-induced aortic de-endothelialization with provision of a platable atherogenic diet to rabbits leads to hyperbetalipoproteinaemia and atherosclerosis rather than to the cholesterol-storage disease which characterized earlier models. Administration of BRL 26314 [ N -(4-chlorobenzyl)- l -phenylalanine] during the induction of atherosclerosis specifically raised high-density lipoprotein (HDL) and decreased the arterial content of cholesterol and collagen in association with reduction in severity of thoracic sudanophilic lesions and intimal-thickening. This anti-atherosclerotic activity was superior to that observed for various standard compounds, and the present studies, using BRL 26314 as a pharmacological tool, provide evidence in vivo for an association between the elevation of HDL and reduction of arterial disease.