Anti-diabetic drug metformin dilates retinal blood vessels through activation of AMP-activated protein kinase in rats
Anti-diabetic drug metformin dilates retinal blood vessels through activation of AMP-activated protein kinase in rats
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DOI：
10.1016/j.ejphar.2017.01.003
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发表时间：
2017-03-05
影响因子：
5
通讯作者：
Nakahara, Tsutomu
中科院分区：
文献类型：
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作者：
Mori, Asami;Ishikawa, Eriko;Nakahara, Tsutomu
这项研究的目的是检查二甲双胍（一种双胍类抗高血糖药物）是否会扩张大鼠的视网膜血管。采用原装高分辨率数字眼底相机在体内采集眼底图像，测量视网膜血管直径。连续记录体表血压和心率。二甲双胍（0.01 ~ 0.3 mg/kg/min）呈剂量依赖性增加视网膜血管直径。二甲双胍的这种视网膜血管扩张作用被化合物C （amp活化蛋白激酶（AMPK）抑制剂）和N-G -硝基- l -精氨酸甲酯（一氧化氮（NO）合成酶抑制剂）所消除。AMPK激活剂5-氨基咪唑-4-羧胺1- β - d -核糖核苷（AICAR, 0.01-1 mg/kg/min）也得到了类似的结果。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合酶的情况下，观察到AICAR有显著的升压反应。这些结果表明，二甲双胍通过激活AMPK使视网膜血管扩张，而NO在AMPK激活后的视网膜血管扩张反应中起重要作用。
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 (0.01-0.3 mg/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-G -nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase. Similar results were obtained with the AMPK activator 5-aminoimidazole-4-carboxamide1-beta-D-ribonucleoside (AICAR, 0.01-1 mg/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.