Sukmawan Renan, Yada Toyotaka, Toyota Eiji, Neishi Yoji, Kume Teruyoshi, Shinozaki Yoshiro, Mori Hidezo, Ogasawara Yasuo, Kajiya Fumihiko, Yoshida Kiyoshi
Department of Cardiology, Kawasaki Medical School, Kurashiki, Japan.
J Pharmacol Sci. 2007 Aug;104(4):341-8. doi: 10.1254/jphs.fp0070186.
We examined whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, exerts its protective effect on coronary microvessels after ischemia/reperfusion (I/R) in vivo. Ninety-minute coronary occlusion followed by reperfusion was performed in 16 open-chest dogs with and without edaravone administration. Coronary small artery (> or = 100 microm in size) and arteriolar (< 100 microm) vasodilation, in the presence of endothelium-dependent (acetylcholine) or -independent (papaverine) vasodilators, was directly observed using intravital microscopy before and after I/R. I/R impaired microvascular vasodilation in response to acetylcholine, whereas administration of edaravone preserved the response in microvessels of both sizes, but to a greater extent in the coronary small arteries. No significant changes were noted with papaverine administration. In the edaravone group, the fluorescent intensity from reactive oxygen species (ROS) was lower, whereas nitric oxide (NO) intensity was higher relative to controls in the microvessels of the ischemic area. In conclusion, edaravone preserves coronary microvascular endothelial function after I/R in vivo. These effects, which were NO-mediated, were attributed to the ROS scavenging properties of edaravone.
我们研究了自由基清除剂依达拉奉（3-甲基-1-苯基-2-吡唑啉-5-酮）在体内缺血/再灌注（I/R）后是否对冠状动脉微血管发挥保护作用。对16只开胸犬进行90分钟冠状动脉闭塞后再灌注，其中部分犬给予依达拉奉，部分未给予。在I/R前后，使用活体显微镜直接观察冠状动脉小动脉（直径≥100微米）和小动脉（直径<100微米）在存在内皮依赖性（乙酰胆碱）或非依赖性（罂粟碱）血管舒张剂时的血管舒张情况。I/R损害了微血管对乙酰胆碱的血管舒张反应，而给予依达拉奉可保留两种大小微血管的反应，但在冠状动脉小动脉中保留程度更大。给予罂粟碱后未观察到显著变化。在依达拉奉组中，缺血区域微血管中活性氧（ROS）的荧光强度较低，而一氧化氮（NO）强度相对于对照组较高。总之，依达拉奉在体内I/R后可保留冠状动脉微血管内皮功能。这些由NO介导的作用归因于依达拉奉的ROS清除特性。
