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

钾通道和环状核苷酸在人脑动脉血管舒张中的作用

• 批准号: 12470297
• 负责人: ONOUE Hisashi
• 金额: $ 3.39万
• 依托单位: JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470297/
• 关键词: CEREBRALARTERY; VASODILATION; POTASSIUM CHANNELS; CYCLIC NUCLEOTIDE

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

本研究旨在探讨K~+通道和环核苷酸在脑血管扩张机制中的作用。一氧化氮(NO)呈浓度依赖性地引起兔基底动脉环松弛，细胞内环鸟苷酸(OGMP)含量增加。这种松弛可被鸟苷环化酶抑制剂(ODQ)几乎完全消除，并可被钙激活的K~(++)通道阻断剂(Charybutroin；CTX)显著抑制。外源性CGMP(8-bromo-CGMP)和磷酸二酯酶抑制剂(扎普司特)升高内源性CGMP的松弛作用也可被CTX抑制。另一方面，更多外周小动脉的灌流实验结果表明，与大动脉相比，CTX对JJJO的松弛作用更强。此外，ODQ不能完全消除脑小动脉的松弛作用，CTX可进一步抑制残留的松弛作用。这些结果表明…此外，NO在兔脑动脉的松弛作用依赖于cGMP，且至少部分依赖于钙激活的K~(++)通道，而且K~(++)通道在小脑动脉中的作用似乎比大血管更重要。此外，在小脑动脉中，非CGMP激活的K~+通道可能参与了NO的松弛作用机制。蛛网膜下腔出血后脑血管痉挛的诱因之一是氧合血红蛋白对脑动脉的预处理，K~+通道在脑大动脉对NO的松弛反应中的作用增强，而在小血管中作用不明显。到目前为止，我们使用从尸检病例中获得的人脑动脉的经验，正在证实在大血管(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和激活Ca^&lt；2+&gt；激活的K^+通道。另一方面，关于人的大脑小动脉(穿动脉等)，由于很难从尸检材料中获得重复性好的数据，目前还没有得出可靠的结论。较少

项目成果

Iahibasii T., Aiiyama M., OnoueH., et al.: "Can transcranial ultrasonication increase recanalization flow with tissue plasminogen activator?"Stroke. Vol.33. 1399-1404 (2002)

Iahibasii T.、Aiiyama M.、OnoueH. 等人：“经颅超声治疗能否通过组织纤溶酶原激活剂增加血流再通？”中风。

Onoue H.: "The effect of suharachnoid hemorrhage on mechanisms of cerebral arterial relaxation induced by nitric oxide"Cerebral Vasospasm. Vol.15. 203-206 (2000)

Onoue H.：“蛛网膜下腔出血对一氧化氮诱导的脑动脉舒张机制的影响”脑血管痉挛。

Tomii M., Onoue H., et al.: "Microscopic measurement of the root exit zone from central glial myelin to peripheral Schwann cell myelin of facial nerve"J. Neurosurg. (In Press). (2003)

Tomii M.，Onoue H.，等人：“面神经中央胶质髓鞘到周围雪旺细胞髓鞘的根部出口区的显微测量”J。

Tomii M., OnOUR fT et al.: "Microscopic measurement of the root exit zone from central glial myelin to peripheral Schwann cell myelin offacial nerve"J. Neurosurg. (In Press).

Tomii M.，OnOUR fT 等人：“从中央胶质髓磷脂到外周雪旺细胞髓磷脂面神经的根出口区的显微测量”J。

Ishibashi T., Akiyama M., Onoue H., et al.: "Can transcranial ultrasonication increase recanalization flow with tissue plasminogen activator?"Stroke. 33. 1399-1404 (2002)

Ishibashi T.、Akiyama M.、Onoue H. 等人：“经颅超声治疗能否通过组织纤溶酶原激活剂增加血流再通？”中风。