EFFECT OF CHOLESTEROL-SUPPLEMENTED DIET IN HERITABLE HYPERLIPIDEMIC YOSHIDA RATS - FUNCTIONAL AND MORPHOLOGICAL CHARACTERIZATION OF THORACIC AORTA

In this study we have considered the possibility of inducing vascular damage in Yoshida Pittsburg (YOS) rat, an inbred strain which has endo genous hyperlipidemia without vascular atherosclerotic damage. Cholest erol-enriched diet (4% cholesterol plus 1% cholic acid and 0.5% thiour acil) was administered to YOS rats, in order to induce atherogenesis. The results indicate that, despite significant increase in serum (abou t 2-fold) and aortic tissue cholesterol (about 6-fold), no morphologic al damage occurred. A reduction in acetylcholine-mediated relaxation ( of about 37%) was observed. No inhibition of ATP- or sodium nitrite-in duced relaxation, or of contraction induced by norepinephrine was seen . Serum triglyceride concentration did not vary after administration o f a cholesterol-enriched diet. Our results suggest that in heritable h yperlipidemic Yoshida rat, after 2 months of cholesterol-enriched diet , despite increased serum cholesterol levels, no atheromatous plaque d eveloped on the aortic wall. Impaired vascular function and reductions in the response to acetylcholine were related to changed endothelial cell function. Administration of a high cholesterol diet to YOS rat ma y represent a new model of mixed endogenous and exogenous hyperlipidem ia that can resemble many human dislipidemic diseases and therefore ma y become a useful tool for the study of isolated endothelial dysfuncti on.