Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine

We tested if vitamin E, a fat-soluble antioxidant, prevents resistance vess el endothelial dysfunction caused by methionine-induced hyperhomocysteinemi a in humans. Moderate elevations in plasma homocysteine concentrations are associated with atherosclerosis and hypertension. Homocysteine causes endot helial dysfunction possibly through several mechanisms. No previous study h as tested if a fat-soluble antioxidant can prevent endothelial dysfunction caused by experimental hyperhomocysteinemia. Ten healthy subjects participa ted in a 2 X 2 factorial, double-blind crossover study, receiving L-methion ine (100 mg/kg at -6 hours) or vehicle, with and without vitamin E (1,200 I U at -13 hours). Endothelial function of forearm resistance vessels was ass essed using forearm blood flow responses to brachial artery administration of endothelium-dependent and endothelium-independent agents. Forearm resist ance vessel dilatation to acetylcholine was significantly impaired 7 hours after methionine (placebo, 583 +/- 87% vs methionine 30 +/- 68%; p <0.05). Dilatation to bradykinin was also impaired (placebo, 509 +/- 54% vs methion ine 289 +/- 48%; p <0.05). Methionine did not after vasodilatation to the e ndothelium-independent vasodilators, nitroprusside, and verapamil. Methioni ne-induced impairment of resistance vessel dilatation to acetylcholine and bradykinin (p <0.05 vs placebo) was prevented by administration of vitamin E (acetylcholine, p = 0.004; bradykinin, p = 0.004; both vs methionine alon e). Experimentally increasing plasma homocysteine concentrations by oral me thionine rapidly impairs resistance vessel endothelial function in healthy humans and this effect is reversed with administration of the fat-soluble a ntioxidant, vitamin E. (C) 2001 by Excerpta Medica, Inc.