Armstead W M
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H423-6. doi: 10.1152/ajpheart.1996.270.2.H423.
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.
本研究旨在探讨三磷酸腺苷敏感性钾通道（ATP-sensitive K+ channels）在配备闭合式颅窗的新生猪中，在鸟苷3',5'-环一磷酸（cGMP）介导的软脑膜动脉舒张中的作用。硝普钠（SNP）（10(-8)，10(-6) M），一种硝基血管扩张剂，可引起软脑膜动脉舒张，而这种舒张作用会被ATP敏感性钾通道拮抗剂格列本脲（10(-6) M）减弱。以百分比计算，单独使用SNP（10(-6) M）时这些反应为25±1%，而在格列本脲存在的情况下，SNP（10(-6) M）引起的舒张为15±1%（n = 5头猪）。cGMP类似物8-BrcGMP（10(-8)，10(-6) M）引起的舒张同样被格列本脲减弱。SNP诱导的软脑膜舒张伴随着皮质蛛网膜下腔脑脊液（CSF）中cGMP水平升高，并且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。单独使用SNP（10(-6) M）可使CSF中cGMP浓度从407±14升高至956±41 fmol/ml，而在LY-83583存在的情况下，SNP导致的CSF中cGMP浓度为340±13，这与335±23 fmol/ml的对照值无差异（n = 5头猪）。LY-83583使SNP诱导的软脑膜舒张减弱，而8-BrcGMP诱导的舒张则无变化。ATP敏感性钾通道激动剂克罗卡林（10(-8)，10(-6) M）引起的舒张被格列本脲阻断（分别在不存在和存在格列本脲的情况下，克罗卡林10(-6) M引起的舒张为24±1%和5±1%，n = 5）。这些数据表明，ATP敏感性钾通道的激活有助于cGMP介导的软脑膜动脉舒张。
