Low-Dose a-Tocopherol Improves and HighDose a-Tocopherol Worsens Endothelial Vasodilator Function in Cholesterol-Fed Rabbits

Abnormalities in endothelium-dependent arterial relaxation develop early in atherosclerosis and may, in part, result from the effects of modified low-density lipoprotein (LDL) on agonistmediated endothelium-derived relaxing factor (EDRF) release and EDRF degradation. a-Tocopherol (AT) is the main lipidsoluble antioxidant in human plasma and lipoproteins, therefore, we investigated the effects of AT on endothelium-dependent arterial relaxation in male New Zealand White rabbits fed diets containing (a) no additive (controls), (b) 1 % cholesterol (cholesterol group), or 1 % cholesterol with either (c) 1,000 IU/kg chow AT (low-dose AT group) or (d) 10,000 IU/kg chow AT (high-dose AT group). After 28 d, we assayed endothelial function and LDL susceptibility to ex vivo copper-mediated oxidation. Acetylcholine- and A23187-mediated endothelium-dependen