TREATMENT WITH DIMETHYLTHIOUREA PREVENTS IMPAIRED DILATATION OF THE BASILAR ARTERY DURING DIABETES-MELLITUS

The goal of this study was to test the hypothesis that the synthesis/r elease of hydroxyl radical accounts for impaired nitric oxide synthase -dependent 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 ip) in response to nitr ic oxide synthase-dependent agonists (acetylcholine and substance P) a nd a nitric oxide synthase-independent agonist (nitroglycerin). Reacti vity of the basilar artery was measured in untreated nondiabetic and d iabetic rats and in nondiabetic and diabetic rats treated with a daily intraperitoneal injection of dimethylthiourea (DMTU; 50 mg/kg). Injec tion of DMTU was started 48 h after injection of streptozotocin and wa s continued throughout the diabetic period (3-4 wk). Topical applicati on of acetylcholine (0.1, 1.0, and 10 mu M) and substance P (0.1 and 1 .0 mu M) produced similar dilatation of the basilar artery in untreate d and DMTU-treated nondiabetic rats. In untreated diabetic rats, the m agnitude of vasodilation produced by acetylcholine and substance P was significantly less than in untreated nondiabetic rats. However, in DM TU-treated diabetic rats, dilatation of the basilar artery in response to acetylcholine and substance P was similar to that observed in nond iabetic rats. Dilatation of the basilar artery in response to nitrogly cerin was similar in untreated and DMTU-treated nondiabetic and diabet ic rats. These findings suggest that impaired nitric oxide synthase-de pendent dilatation of the basilar artery during diabetes mellitus may be related to the synthesis/release of hydroxyl radical.