Hypotension dilates pial arteries by KATP and Kca channel activation
Hypotension dilates pial arteries by KATP and Kca channel activation
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DOI：
10.1016/s0006-8993(98)01146-9
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发表时间：
1999-01-16
期刊：
影响因子：
2.9
通讯作者：
Armstead, WM
中科院分区：
文献类型：
--
作者：
Armstead, WM
低血压引起的新生猪软脑膜动脉扩张是胰高血糖素依赖性的。前列腺素又通过cGMP和cAMP依赖性机制引起血管舒张，并且K（+）通道活化有助于环核苷酸诱导的血管舒张。本研究旨在表征ATP敏感性（K（ATP））和钙敏感性（K（ca））通道激活在低血压诱导的新生猪软脑膜动脉扩张中的作用。格列本脲和伊比利亚毒素、K（ATP）和K（Ca）通道拮抗剂可减弱低血压诱导的扩张（伊比利亚毒素前后分别为36 +/- 1和14 +/- 2%）。联合使用这些K（+）通道拮抗剂可消除血管反应。低血压诱导的扩张与脑脊液（CSF）cAMP浓度升高相关，但与cGMP浓度无关（cAMP为1023 +/- 29 vs. 1566 +/- 39 fmol/ml）。一氧化氮（NO）合酶抑制剂L-NNA和蛋白激酶G抑制剂Rp 8-Br cGMP没有作用，但蛋白激酶A抑制剂Rp 8-Br cAMP减弱了膨胀性扩张（Rp 8-Br cAMP前后分别为35 +/- 1和16 +/- 2%）。cAMP类似物8-溴cAMP（10（-8），10（-6）M）的扩张作用被格列本脲和伊比利亚毒素减弱（8 +/- 1和17 +/- 1 vs.格列本脲前后4 +/- 1和9 +/- 1%）。这些数据表明，K（ATP）和K（Ca）通道激活有助于低血压诱导的扩张。这些数据表明，低血压期间的扩张是由依序释放的肾上腺素和cAMP引起的，这反过来又激活了K（ATP）和K（Ca）通道。(C)1999 Elsevier Science B. V.保留所有权利。
Hypotension induced pial artery dilation is prostaglandin-dependent in the newborn pig. Prostaglandins, in turn, elicit vasodilation through cGMP and cAMP dependent mechanisms and K(+) channel activation contributes to cyclic nucleotide induced vasodilation. The present study was designed to characterize the role of ATP sensitive (K(ATP)) and calcium sensitive (K(ca)) channel activation in hypotension induced pial artery dilation in newborn pigs equipped with a closed cranial window. Glibenclamide and iberiotoxin, K(ATP) and K(ca) channel antagonists, attenuated hypotension induced dilation (36 +/- 1 vs. 14 +/- 2% before and after iberiotoxin). Combined administration of these K(+) channel antagonists eliminated the vascular response. Hypotension induced dilation was associated with elevated cerebrospinal fluid (CSF) cAMP but not cGMP concentration (1023 +/- 29 vs. 1566 +/- 39 fmol/ml for cAMP). L-NNA, a nitric oxide (NO) synthase inhibitor, and Rp 8-Br cGMPs, a protein kinase G inhibitor, had no effect but Rp 8-Br cAMPs, a protein kinase A inhibitor, attenuated hypotensive dilation (35 +/- 1 vs. 16 +/- 2% before and after Rp 8-Br cAMPs). Dilation by the cAMP analogue 8-Bromo cAMP (10(-8), 10(-6) M) was attenuated by glibenclamide and iberiotoxin (8 +/- 1 and 17 +/- 1 vs. 4 +/- 1 and 9 +/- 1% before and after glibenclamide). These data show that both K(ATP) and K(ca) channel activation contribute to hypotension induced dilation. These data suggest that dilation during hypotension results from the sequential release of prostaglandins and cAMP, which, in turn, activates both the K(ATP) and K(ca) channel. (C) 1999 Elsevier Science B.V. All rights reserved.