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

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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