Effect of Chronic Treatment with Vitamin E on Endothelial Dysfunction in a Type I in Vivo Diabetes Mellitus Model and in Vitro

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Abstract
Diabetes mellitus often leads to generalized vasculopathy. Because of the pathophysiological role of free radicals we investigated the effects of vitamin E. Twenty-eight rats were rendered diabetic by streptozotocin injection and were fed either with a diet with low (10 mg/kg of chow), medium (75 mg/kg of chow) or high amounts of vitamin E (1300 mg/kg of chow). Nine age-matched nondiabetic rats receiving 75 mg of vitamin E/kg chow served as controls. After 7 months, mesenteric microcirculation was investigated. Smooth muscle contractile function was not altered in diabetic versus nondiabetic vessels. Endothelial function was significantly reduced in diabetics; relaxation upon 1 μM acetylcholine was reduced by 50% in diabetics with a medium and high vitamin E diet. In vitamin E-deprived rats, a complete loss of endothelium-dependent relaxation was observed, and instead, acetylcholine elicited vasoconstriction.l-NG-Nitro-arginine-induced vasoconstriction was reduced in small arteries in diabetics, which was not prevented by vitamin E, but was aggravated by vitamin E deprivation. In a subchronic endothelial cell culture model, cells were cultivated with 5 or 20 mM d-glucose for an entire cell culture passage (4 days) with or without vitamin E (20 mg/l versus 0.01 mg/l). Hyperglycemia led to significant reduction in basal and ATP-stimulated nitric oxide (NO)-production. Hyperglycemia-induced reduction in basal NO-release was significantly prevented by vitamin E, whereas reduction in stimulated NO-release was not influenced. NADPH-diaphorase activity was reduced by 40% by hyperglycemia, which was completely prevented by vitamin E. We conclude that 1) vitamin E has a potential to prevent partially hyperglycemia-induced endothelial dysfunction, 2) under in vivo conditions vitamin E deficiency enhanced diabetic endothelial dysfunction dramatically, and 3) positive effects of vitamin E may be attenuated with a longer disease duration.

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