Role of ATP-sensitive K+ channels in cGMP-mediated pial artery vasodilation
Role of ATP-sensitive K+ channels in cGMP-mediated pial artery vasodilation
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DOI：
10.1152/ajpheart.1996.270.2.h423
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发表时间：
1996-02-01
影响因子：
4.8
通讯作者：
Armstead, WM
中科院分区：
文献类型：
--
作者：
Armstead, WM
本研究旨在探讨atp敏感的K+通道在鸟苷3',5'-环单磷酸酯（cGMP）介导的新生猪颅窗关闭时动脉血管舒张中的作用。硝普钠（SNP） (10（-8), 10(-6) M）是一种硝基血管扩张剂，可引起冠状动脉扩张，并被atp敏感的K+通道拮抗剂格列本脲（10(-6)M）减弱。在百分比基础上，SNP （10(-6) M）单独存在时，这些反应为25 +/- 1%，而格列本脲存在时，SNP （10(-6) M）的反应为15 +/- 1% （n = 5头猪）。cGMP类似物8-BrcGMP (10（-8), 10(-6) M）产生的扩张同样被格列本脲减弱。snp诱导的心梗扩张伴随着皮质蛛网膜周围脑脊液（CSF） cGMP水平的升高，这些生化变化被可溶性鸟苷酸环化酶抑制剂LY-83583 （10(-5) M）阻断。单独的SNP （10(-6) M）使CSF cGMP浓度从407 +/- 14增加到956 +/- 41 fmol/ml，而LY-83583存在的SNP使CSF cGMP浓度为340 +/- 13，与对照组的335 +/- 23 fmol/ml （n = 5头猪）没有差异。snp诱导的心梗扩张被LY-83583减弱，而8- brcgmp诱导的心梗扩张没有变化。Cromakalim (10（-8), 10(-6) M）是一种atp敏感的K+通道激动剂，在格列本脲不存在和不存在的情况下，Cromakalim （10(- 6) M）产生的扩张被格列本脲阻断（分别为24 +/- 1比5 +/- 1%，n = 5）。这些数据表明atp敏感的K+通道的激活有助于cgmp介导的头动脉扩张。
The present study was designed to investigate the role of ATP-sensitive K+ channels in guanosine 3',5'-cyclic monophosphate (cGMP)-mediated pial artery vasodilation in newborn pigs equipped with a closed cranial window. Sodium nitroprusside (SNP) (10(-8), 10(-6) M), a nitrovasodilator, elicited pial artery dilation that was attenuated by the ATP-sensitive K+ channel antagonist glibenclamide (10(-6) M). On a percentage basis, these responses were 25 +/- 1% for the presence of SNP (10(-6) M) alone, whereas 15 +/- 1% dilation was observed for SNP (10(-6) M) in the presence of glibenclamide (n = 5 pigs). Dilation produced by the cGMP analogue, 8-BrcGMP (10(-8), 10(-6) M), was similarly attenuated by glibenclamide. SNP-induced pial dilation was accompanied by increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP levels, and these biochemical changes were blocked by the soluble guanylate cyclase inhibitor, LY-83583 (10(-5) M). SNP (10(-6) M) alone increased CSF cGMP concentration from 407 +/- 14 to 956 +/- 41 fmol/ml, whereas SNP in the presence of LY-83583 yielded a CSF cGMP concentration of 340 +/- 13, which was no different from the control value of 335 +/- 23 fmol/ml (n = 5 pigs). SNP-induced pial dilation was blunted by LY-83583, whereas 8-BrcGMP-induced dilation was unchanged. Cromakalim (10(-8), 10(-6) M), an ATP-sensitive K+ channel agonist, produced dilation that was blocked by glibenclamide (24 +/- 1 vs. 5 +/- 1% for cromakalim 10(-6) M, in the absence and presence of glibenclamide, respectively, n = 5). These data indicate that activation of ATP-sensitive K+ channels contribute to cGMP-mediated pial artery dilation.