Vitamin E reverses cholesterol-induced endothelial dysfunction in the rabbit coronary circulation

Hypercholesterolaemia and atherosclerosis are associated with impaired endothelium-dependent vasodilation. In this study we have examined the effects of vitamin E on cholesterol-induced endothelial dysfunction in the rabbit coronary circulation. Rabbits were maintained for 4 or 8 weeks on one of three experimental diets: (a) control chow, (b) 1% cholesterol or (c) 1% cholesterol for the first half of the treatment period followed by 1% cholesterol + 0.2% vitamin E during the last half of the treatment. After sacrifice, vasodilator responses to acetylcholine and sodium nitroprusside in the isolated perfused heart were studied. Responses to sodium nitroprusside were similar between the groups whereas responses to acetylcholine were significantly impaired in cholesterol-fed rabbits after both 4 and 8 weeks when compared to controls. In the cholesterol + vitamin E group, responses to acetylcholine were similar to controls and significantly greater than in the group receiving cholesterol alone. These results show that both 4 and 8 weeks of cholesterol-feeding induces an endothelial dysfunction in the coronary circulation of the rabbit, and that vitamin E protects against this dysfunction. By comparing responses to acetylcholine in the 4 week cholesterol group with the 8 week cholesterol + vitamin E group it was shown that vitamin E may not only prevent further deterioration of the endothelial function in the rabbit heart, but may also reverse the adverse effects of hypercholesterolaemia.