INFLUENCE OF 0.1-PERCENT OR 0.2-PERCENT CHOLESTEROL-ENRICHED DIETS ONTHE INDUCTION OF ATHEROSCLEROSIS AND AORTA REACTIVITY IN-VITRO

Current knowledge of atherogenesis is largely based on animal models o f hypercholesterolemia, which rarely show changes similar to the lesio ns described in humans. We studied the influence of two law cholestero l-enriched diets on the development of anatomopathologic lesions and o n Me reactivity of the isolated aorta in rabbits. Compared with contro ls (rabbits fed a normal diet), a 0.1% cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5-hydroxytryptamine ( 5-HT)-induced contractile responses, as well as a decreases in acetylc holine (ACh)induced relaxing response (endothelium-dependent, through the production of NO). Noradrenaline (NA)-induced contractions and rel axations elicited by sodium nitroprusside (SNP: endothelium independen t) were not significantly modified. Because at 6 months, significant a natomopathologic intimal early lesions were not found, functional endo thelial changes can explain such findings. There was a defect in NO sy nthesis, release, or diffusion: 5 I-IT, but not NA, may be responsible for inducing NO production. In 0.2% cholesterol-fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile responses were found. In both cases, there was a decrease of ACh-induced relaxing ef fect, whereas responses to SNP remained unchanged. Intimal early and a dvanced lesions were present at both the 4- and 12-week periods. These data suggest abnormalities of the NO system. The effects obtained wit h NA may be explained by a possible decrease of catechol-O-methyltrans ferase, (COMT) or monoamine oxidase (MAO) activities or both or by dec reased amine uptake. The extent to which NA may induce NO production i s small, because changes in NA-induced contractions are verified only in the presence of significant alterations in the endothelium. The use of a 0.2% cholesterol diet for a short time may induce atheroscleroti c lesions, whereas the 0.1% cholesterol diet for a 9-month period, bes ides being closer to the human diet, allows the detection of functiona l abnormalities before the evidence of structural lesions.