Endothelial dysfunction, lipid peroxidation and cholesterol level in rabbit arteries: relationship to progressive hypercholesterolemia

Objective. The aim of this study was to evaluate the influence of a gradual increase in the plasma total cholesterol concentration and of lipid peroxidation on endothelial function in rabbit arteries. Material and methods. Fifty male New Zealand white rabbits were fed a diet enriched with 0.5% cholesterol and 10% coconut oil and were allocated to one of nine groups (G2 to G10) based on sequential determinations of their plasma total cholesterol concentration (each group covered an interval of 100 mg/dL). The control group (G1) consisted of five rabbits fed a non-supplemented diet. The rabbits were killed at the end of the treatment and the total plasma cholesterol concentration, arterial wall cholesterol level and lipid peroxidation based on the quantification of malondialdehyde were determined using commercial kits. Endothelial function was assessed based on concentration-response curves to acetylcholine and sodium nitroprusside in aortic segments. Results: Treatment with a cholesterol-rich diet resulted in disproportional increases in the arterial wall cholesterol concentration, lipid peroxidation and a disproportional decrease in the maximum endothelium-dependent relaxations in relation to the plasma total cholesterol concentration. However, the maximum endothelium-dependent relaxations were proportional to the increase in the arterial wall content of malondialdehyde. Conclusions. These results show that the levels of arterial wall cholesterol, lipid peroxidation and endothelial dysfunction are not proportional to the degree of hypercholesterolemia, although endothelial dysfunction is proportional to the extent of lipid peroxidation in the vessel wall.