1. Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (NO) dilator system in patients with hypercholesterolaemia. 2. Seven subjects aged 47+/-3 (+/-S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0+/-0.1 mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal NO function was assessed by infusion of NG-monomethyl-L-arginine. 3. Plasma alpha-tocopherol concentration was enhanced after administration of vitamin E (34.6+/-1.8 to 86.9+/-9.6 micromol/l; P<0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P<0. 01), forearm vascular resistance (P<0.05) or forearm blood flow ratios (P<0.001). Similarly, absolute forearm blood flow (P<0.05), forearm vascular resistance (P<0.01) and forearm blood flow ratio (P<0.01) responses to NG-monomethyl-L-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered. 4. These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated NO-related endothelial function in subjects with hypercholesterolaemia.
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