Superoxide dismutase ameliorates impaired nitric oxide synthase-dependent dilatation of the basilar artery during chronic alcohol consumption.

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.