title: Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
abstract: We examined the responses of basilar arteries taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model. Both the nitric oxide (NO)-mediated relaxation and the cyclic 3',5'-guanosine monophosphate (cGMP) production elicited by acetylcholine (ACh) were much weaker in OLETF rats than in age-matched control Long Evans Tokushima Otsuka (LETO) rats. The contraction induced by an NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine (L-NNA)] was weaker in the OLETF group. In that group, application of apocynin, an NAD(P)H oxidase inhibitor, normalized (i) ACh-induced relaxation, (ii) L-NNA-induced contraction, and (iii) ACh-induced cGMP production to the LETO levels. Superoxide anion production was greater in basilar arteries from OLETF rats than in those from LETO rats. The protein expression of gp91(phox), an NAD(P)H oxidase subunit, was upregulated in the OLETF arteries (versus LETO ones). These results suggest that the existence of endothelial dysfunction in basilar arteries in type 2 diabetes is related to increased oxidative stress mediated via NAD(P)H oxidase. Possibly, an impairment of NO-dependent relaxation responses and a basal impairment of NO signaling may be responsible for the increased risk of adverse cerebrovascular events in type 2 diabetes.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wachi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Seyama
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D001488:Basilar Artery / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D051381:Rats; D020334:Rats, Inbred OLETF; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents; D014664:Vasodilation / Q000502:physiology
chemical_list: D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; C056165:acetovanillone; D019001:Nitric Oxide Synthase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000109:Acetylcholine