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/release 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 nitric oxide synthase-dependent agonists (acetylcholine and substance P) and a nitric oxide synthase-independent agonist (nitroglycerin). Reactivity of the basilar artery was measured in untreated nondiabetic and diabetic rats and in nondiabetic and diabetic rats treated with a daily intraperitoneal injection of dimethylthiourea (DMTU; 50 mg/kg). Injection of DMTU was started 48 h after injection of streptozotocin and was continued throughout the diabetic period (3-4 wk). Topical application of acetylcholine (0.1, 1.0, and 10 microM) and substance P (0.1 and 1.0 microM) produced similar dilatation of the basilar artery in untreated and DMTU-treated nondiabetic rats. In untreated diabetic rats, the magnitude of vasodilation produced by acetylcholine and substance P was significantly less than in untreated nondiabetic rats. However, in DMTU-treated diabetic rats, dilatation of the basilar artery in response to acetylcholine and substance P was similar to that observed in nondiabetic rats. Dilatation of the basilar artery in response to nitroglycerin was similar in untreated and DMTU-treated nondiabetic and diabetic rats. These findings suggest that impaired nitric oxide synthase-dependent dilatation of the basilar artery during diabetes mellitus may be related to the synthesis/release of hydroxyl radical.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Patel
K P
KP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013373:Substance P / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D013373:Substance P; D013311:Streptozocin; C038983:1,3-dimethylthiourea; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D013890:Thiourea; D000109:Acetylcholine