Mayhan W G, Patel K P
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Am J Physiol. 1998 Jun;274(6):H1895-901. doi: 10.1152/ajpheart.1998.274.6.H1895.
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.
糖尿病期间，羟基自由基的合成/释放是导致一氧化氮合酶依赖性基底动脉扩张受损的原因。我们在非糖尿病和糖尿病大鼠（腹腔注射链脲佐菌素，50 - 60 mg/kg）体内测量了基底动脉的直径，以响应一氧化氮合酶依赖性激动剂（乙酰胆碱和P物质）和一氧化氮合酶非依赖性激动剂（硝酸甘油）。在未治疗的非糖尿病和糖尿病大鼠以及每天腹腔注射二甲基硫脲（DMTU；50 mg/kg）的非糖尿病和糖尿病大鼠中测量基底动脉的反应性。在注射链脲佐菌素48小时后开始注射DMTU，并在整个糖尿病期（3 - 4周）持续注射。局部应用乙酰胆碱（0.1、1.0和10 microM）和P物质（0.1和1.0 microM）在未治疗和DMTU治疗的非糖尿病大鼠中引起基底动脉类似的扩张。在未治疗的糖尿病大鼠中，乙酰胆碱和P物质引起的血管舒张幅度明显小于未治疗的非糖尿病大鼠。然而，在DMTU治疗的糖尿病大鼠中，基底动脉对乙酰胆碱和P物质的扩张与非糖尿病大鼠中观察到的相似。未治疗和DMTU治疗的非糖尿病和糖尿病大鼠中，基底动脉对硝酸甘油的扩张相似。这些发现表明，糖尿病期间一氧化氮合酶依赖性基底动脉扩张受损可能与羟基自由基的合成/释放有关。
