title: Effect of chronic treatment with vitamin E on endothelial dysfunction in a type I in vivo diabetes mellitus model and in vitro.
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 micro M 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-N(G)-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.
authors.affiliation: University of Leipzig, Heart Centre Leipzig, Clinic for Cardiac Surgery, Leipzig, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dhein
authors.forename: A
authors.initials: A
authors.lastname: Kabat
authors.forename: A
authors.initials: A
authors.lastname: Olbrich
authors.forename: P
authors.initials: P
authors.lastname: Rösen
authors.forename: H
authors.initials: H
authors.lastname: Schröder
authors.forename: F-W
authors.initials: FW
authors.lastname: Mohr
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D013311:Streptozocin; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D009569:Nitric Oxide; D013311:Streptozocin