Nakazawa Taisuke, Kaneko Yoshiko, Mori Asami, Saito Maki, Sakamoto Kenji, Nakahara Tsutomu, Ishii Kunio
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Vascul Pharmacol. 2007 Mar;46(3):153-9. doi: 10.1016/j.vph.2006.09.002. Epub 2006 Sep 23.
Diabetes alters retinal hemodynamics, but little is known about the impact of diabetes on the role of endothelium-derived hyperpolarizing factor (EDHF) in the regulation of retinal circulation. Therefore, we examined how diabetes affects the nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine. Male Wistar rats were treated with streptozotocin (80 mg/kg, i.p.) and experiments were performed 6-8 weeks later. Under artificial ventilation, rats were treated with tetrodotoxin (100 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. Methoxamine was used to maintain adequate systemic circulation. Fundus images were captured by a digital camera that was equipped with a special objective lens. The vasodilator responses of retinal arterioles were assessed by measuring changes in diameters of the vessels. In streptozotocin-induced diabetic rats and the age-matched controls, acetylcholine increased diameters of retinal arterioles in a dose-dependent manner. The vasodilator responses to acetylcholine in diabetic rats were smaller than those in control rats. The nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles observed under treatment with combination of N(G)-nitro-l-arginine methyl ester (30 mg/kg, i.v.) and indomethacin (5 mg/kg, i.v.) were also attenuated by diabetes. Diabetes did not alter the dilator responses of retinal arterioles to sodium nitroprusside and forskolin. These results suggest that diabetes impairs EDHF-mediated vasodilation of retinal arterioles induced by acetylcholine. The impaired EDHF-mediated vasodilation may contribute to alteration of retinal hemodynamics in diabetes.
糖尿病会改变视网膜血流动力学，但对于糖尿病对内皮源性超极化因子（EDHF）在视网膜循环调节中作用的影响却知之甚少。因此，我们研究了糖尿病如何影响乙酰胆碱诱导的视网膜小动脉不依赖一氧化氮和前列腺素的血管舒张。雄性Wistar大鼠腹腔注射链脲佐菌素（80 mg/kg），6 - 8周后进行实验。在人工通气条件下，给大鼠静脉注射河豚毒素（100 μg/kg）以消除任何神经活动并防止眼球运动。用甲氧明维持适当的体循环。用配备特殊物镜的数码相机拍摄眼底图像。通过测量血管直径的变化来评估视网膜小动脉的血管舒张反应。在链脲佐菌素诱导的糖尿病大鼠和年龄匹配的对照组中，乙酰胆碱以剂量依赖的方式增加视网膜小动脉的直径。糖尿病大鼠对乙酰胆碱的血管舒张反应小于对照大鼠。在用N(G)-硝基-L-精氨酸甲酯（30 mg/kg，静脉注射）和吲哚美辛（5 mg/kg，静脉注射）联合处理下观察到的视网膜小动脉不依赖一氧化氮和前列腺素的血管舒张也因糖尿病而减弱。糖尿病并未改变视网膜小动脉对硝普钠和福斯高林的舒张反应。这些结果表明，糖尿病损害了乙酰胆碱诱导的视网膜小动脉EDHF介导的血管舒张。EDHF介导的血管舒张受损可能导致糖尿病患者视网膜血流动力学的改变。
