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）诱导兔基底动脉环松弛，细胞内循环gmp （OGMP）含量呈浓度依赖性增加。鸟苷酸环化酶抑制剂（ODQ）几乎完全消除松弛，Ca^<2+>-活化的K^+通道阻滞剂（charybutroxin； CTX）显著抑制松弛。外源性CGMP（8-溴-CGMP）和提高内源性CGMP水平的磷酸二酯酶抑制剂（zaprinast）诱导的松弛也被CTX抑制。另一方面，灌注实验结果表明，与大动脉相比，CTX对JJJO的松弛作用更强。此外，ODQ并没有完全消除大脑小动脉的松弛，剩余的松弛被CTX进一步抑制。这些结果表明，NO在兔脑动脉中的松弛作用是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^+通道在脑小动脉中的作用似乎比在大血管中的作用更重要。此外，在脑小动脉中，不依赖cgmp的K^+通道激活可能参与了NO的松弛作用机制。脑动脉预处理氧合血红蛋白（被认为是蛛网膜下腔出血后脑血管痉挛的致病物质之一）可增加大脑血管中K^+通道对NO的舒张反应，而在小血管中则无作用。到目前为止，我们使用从尸体解剖病例中获得的人类大脑动脉进行的实验，正在证明在大血管（大脑基底动脉和大脑中动脉）中，NO的松弛作用似乎依赖于cGMP和Ca^<2+>激活的K^+通道的激活。另一方面，关于人类大脑小动脉（穿孔动脉等），由于难以从死后材料中获得良好的可重复性数据，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