title: Superoxide dismutase ameliorates impaired nitric oxide synthase-dependent dilatation of the basilar artery during chronic alcohol consumption.
abstract: The goals of this study were to determine whether chronic alcohol consumption impairs nitric oxide synthase-dependent reactivity of the basilar artery and to determine a potential mechanism which might account for the effects of alcohol on the basilar artery. Sprague-Dawley rats were fed liquid diets with or without alcohol for 8 weeks. Using intravital microscopy, we measured the diameter of basilar artery in response to nitric oxide synthase-dependent agonists (acetylcholine and bradykinin) and a nitric oxide synthase-independent agonist (nitroglycerin). Topical application of acetylcholine (0.1 and 1 microM) and bradykinin (1 and 10 nM) produced dose-related dilatation of the basilar artery in non-alcohol-fed and alcohol-fed rats. However, the magnitude of vasodilatation in response to acetylcholine and bradykinin was significantly less in alcohol-fed rats compared to non-alcohol-fed rats. Dilatation of the basilar artery in response to nitroglycerin was similar in non-alcohol-fed and alcohol-fed rats. Next, we examined whether impaired responses of the basilar artery in alcohol-fed rats in response to acetylcholine and bradykinin may be related to the production of oxygen radicals. We found that topical application of superoxide dismutase (150 U/ml) significantly improved impaired receptor-mediated nitric oxide synthase-dependent dilatation of basilar artery in alcohol-fed rats. However, superoxide dismutase did not alter responses of the basilar artery to nitroglycerin in alcohol-fed rats, and did not alter responses of the basilar artery to nitric oxide synthase-dependent or -independent agonists in non-alcohol-fed rats. Our findings suggest that chronic consumption of alcohol impairs nitric oxide synthase-dependent dilatation of a large cerebral artery which may be related to the receptor-mediated release of oxygen radicals to inactivate nitric oxide.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000428:Alcohol Drinking / Q000009:adverse effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals / Q000009:adverse effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D005609:Free Radicals; D000431:Ethanol; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin