ROLE OF POTASSIUM CHANNELS AND CYCLIC NUCLEOTIDES IN VASODILATION OF HUMAN CEREBRAL ARTERIES

本研究旨在探讨K^+通道和环核苷酸在脑动脉血管舒张机制中的作用。一氧化氮（NO）供体可使兔基底动脉环舒张，并依赖性地增加细胞内环GMP（OGMP）含量。鸟苷酸环化酶抑制剂（ODQ）几乎完全消除这种舒张作用，钙激活钾通道阻断剂（charybutroxin; CTX）则显著抑制这种舒张作用。由外源性CGMP（8-溴-CGMP）和磷酸二酯酶抑制剂（zaprinast），提高内在的CGMP水平诱导的舒张，也被CTX抑制。另一方面，在灌注实验下，具有更多外周小动脉的结果表明，与大动脉相比，CTX对JJJO的舒张作用更强烈地抑制。此外，ODQ不能完全消除脑小动脉的舒张作用，CTX可进一步抑制其舒张作用。这些结果表明 ...更多信息 NO对兔脑动脉的舒张作用是cGMP依赖性的，至少部分依赖于Ca^2+激活的K^+通道的激活，并且K ^+通道在小动脉中的作用似乎比在大动脉中更重要。此外，我们还认为，在脑小动脉中，非cGMP依赖性K^+通道激活可能参与了NO的舒张作用机制。用氧合血红蛋白（被认为是蛛网膜下腔出血后脑血管痉挛的一种致病物质）预处理脑动脉，可增强K^+通道在脑大动脉对NO的舒张反应中的作用，而在小动脉中则无此作用。迄今为止，我们的实验使用的是从尸体解剖中获得的人脑动脉，这些实验正在进一步证实，在大血管（基底动脉和大脑中动脉）中，NO的舒张作用似乎依赖于cGMP和Ca^2+激活的K^+通道的激活。另一方面，关于人的小脑动脉（穿通动脉等），由于难以从尸检材料中获得可重复性好的数据，因此尚未得出可靠的结论。少

This study was designed to investigate the role of K^+ channels and cyclic nucleotides in vasodilation mechanisms in cerebral arteries. Nitric oxide (NO) donorinduced relaxation ofrabbitbasilar arterial ring , and increased intraceilular cyclic-GMP (OGMP) content coneentration-dependantly. The relaxation was almost completely abolished by guanylate cyclase inhibitor (ODQ), and was significantly inhibited by Ca^<2+>-activated K^+ channel blocker (charybutroxin; CTX). Relaxations induced by extrinsic CGMP (8-bromo-CGMP) and phosphodiesterase inhibitor (zaprinast), which elevates intrinsic CGMP level, were also inhibited by CTX. On the other hand, results with more peripheral small arteries under purfusion experiments, indicated that relaxations to JJJO were more strongly inhibited by CTX compared to large arteries. In addition, the relaxation in Small cerebral arteries was not completely abolished by ODQ, and the remaining relaxation was further inhibited by CTX . These results indicate … More that relaxant action of NO in rabbit cerebral arteries is cGMP-dependent and atleast partly dependent on activation of Ca^<2+>-activated K^+ channels, and that the role ofK^+ channels seems moreimportantin small cerebral arteries than inlargevessels. Furthermore,it should be suggested that in small cerebral arteries CGMP-independent activation of K^+ channels might be involved in relaxant mechanisms of action of NO. Pretreatment of cerebral arteries with oxyhemoglobin, which is regarded as an one causative substance for cerebral vasjospasm after subarachnoid hemorrhage, increased role of K^+ channels in relaxation response to NO in large cerebral arteries but not in small vessels. Our experiements so far, using human cerebral arteries obtained from autopsy casas, are closing up the evidence that in large vessels (the basilar and middle cerebral arteries) the relaxant action of NO seems to dependent on cGMP and activation of Ca^<2+>-activated K^+ channels. On the other hand, concerning about small human cerebral arteries (perforating arteri.esetc.), reliable conclusions have not yet been drawn because of difficulties to obtain well reproducible data from postmortem materials. Less