SUPEROXIDE-DISMUTASE PARTIALLY RESTORES IMPAIRED DILATATION OF THE BASILAR ARTERY DURING DIABETES-MELLITUS

The goal of this study was to test the hypothesis that administration of superoxide dismutase restores nitric oxide synthase-mediated dilata tion of the basilar artery during diabetes mellitus. We measured the d iameter of the basilar artery in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg i.p.) in response to nitric oxide syntha se-dependent agonists (acetylcholine and bradykinin) and a nitric oxid e synthase-independent agonist (nitroglycerin) before and during appli cation of superoxide dismutase. Topical application of acetylcholine ( 1.0 and 10 mu M) and bradykinin (1.0 and 10 mu M) produced dose-relate d dilatation of the basilar artery in nondiabetic and diabetic rats. H owever, the magnitude of vasodilation produced by acetylcholine and br adykinin was significantly less in diabetic rats. Topical application of nitroglycerin (0.1 and 1.0 mu M) produced similar dose-related dila tation of the basilar artery in nondiabetic and diabetic rats. Treatme nt with superoxide dismutase (150 U/ml) did not alter baseline diamete r of the basilar artery in nondiabetic and diabetic rats. However, top ical application of superoxide dismutase partially restored nitric oxi de synthase-dependent dilatation of the basilar artery in diabetic rat s towards that observed in nondiabetic rats. Superoxide dismutase did not alter dilatation of the basilar artery in nondiabetic rats. These findings suggest that impaired nitric oxide synthase-dependent dilatat ion of the basilar artery during diabetes mellitus may be related, in part, to enhanced release of oxygen-derived free radicals.