Mori Asami, Ishikawa Eriko, Amano Tomoyo, Sakamoto Kenji, Nakahara Tsutomu
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Eur J Pharmacol. 2017 Mar 5;798:66-71. doi: 10.1016/j.ejphar.2017.01.003. Epub 2017 Jan 10.
The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and N-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase. Similar results were obtained with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR, 0.01-1mg/kg/min). Neither metformin nor AICAR exerted significant effect on mean blood pressure and heart rate. However, a significant pressor response to AICAR was observed upon inhibition of NO synthase. These results suggest that metformin dilates retinal blood vessels through activation of AMPK, and NO plays an important role in the retinal vasodilator response following AMPK activation.
本研究的目的是检测双胍类抗高血糖药物二甲双胍是否能扩张大鼠视网膜血管。使用原装高分辨率数字眼底相机在体内采集眼底图像，并测量视网膜血管直径。连续记录全身血压和心率。二甲双胍（0.01 - 0.3mg/kg/min）以剂量依赖方式增加视网膜血管直径。二甲双胍的这种视网膜血管舒张作用被AMP激活蛋白激酶（AMPK）抑制剂化合物C和一氧化氮（NO）合酶抑制剂N - 硝基 - L - 精氨酸甲酯消除。使用AMPK激活剂5 - 氨基咪唑 - 4 - 甲酰胺 - 1 - β - D - 核糖核苷（AICAR，0.01 - 1mg/kg/min）也得到了类似结果。二甲双胍和AICAR对平均血压和心率均无显著影响。然而，在抑制NO合酶后，观察到对AICAR有显著的升压反应。这些结果表明，二甲双胍通过激活AMPK扩张视网膜血管，并且NO在AMPK激活后的视网膜血管舒张反应中起重要作用。
