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 dilatation of the basilar artery during diabetes mellitus. We measured the diameter of the basilar artery in vivo in nondiabetic and diabetic rats (streptozotocin; 50-60 mg/kg i.p.) in response to nitric oxide synthase-dependent agonists (acetylcholine and bradykinin) and a nitric oxide synthase-independent agonist (nitroglycerin) before and during application of superoxide dismutase. Topical application of acetylcholine (1.0 and 10 microM) and bradykinin (1.0 and 10 microM) produced dose-related dilatation of the basilar artery in nondiabetic and diabetic rats. However, the magnitude of vasodilation produced by acetylcholine and bradykinin was significantly less in diabetic rats. Topical application of nitroglycerin (0.1 and 1.0 microM) produced similar dose-related dilatation of the basilar artery in nondiabetic and diabetic rats. Treatment with superoxide dismutase (150 U/ml) did not alter baseline diameter of the basilar artery in nondiabetic and diabetic rats. However, topical application of superoxide dismutase partially restored nitric oxide synthase-dependent dilatation of the basilar artery in diabetic rats 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 dilatation of the basilar artery during diabetes mellitus may be related, in part, to enhanced release of oxygen-derived free radicals.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198, USA.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000503:physiopathology; D001920:Bradykinin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin