Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations
Role of endothelial intermediate conductance KCa channels in cerebral EDHF-mediated dilations
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DOI：
10.1152/ajpheart.00376.2003
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发表时间：
2003-10-01
影响因子：
4.8
通讯作者：
Hunte, MS
中科院分区：
文献类型：
--
作者：
Marrelli, SP;Eckmann, MS;Hunte, MS
本研究评价了内皮细胞中电导钙敏感性钾通道（IKCa）在加压脑动脉内皮源性超极化因子（EDHF）介导的扩张机制中的作用。将雄性大鼠大脑中动脉（MCA）固定在分离的血管室中，加压（85 mmHg），并管腔灌注（100穆尔/min）。同时测量动脉直径和内皮细胞内Ca 2+浓度（[Ca 2 +]（i）; fura-2）或内皮膜电位[4-{2-[6-（二辛基氨基）-2-萘基]乙烯基} 1-（3-磺丙基）-吡啶鎓（二-8-ANEPPS）]的变化。一氧化氮合酶和环氧合酶抑制剂始终存在。腔应用UTP产生EDHF介导的扩张，与显着的内皮超极化。的扩张和内皮超极化几乎被废除的IKCa通道的抑制剂，但不是由选择性抑制剂的小或大电导K-Ca通道（apamin和伊比利亚毒素，分别）。此外，用1-乙基-2-苯并咪唑啉酮（1-EBIO）直接刺激内皮IKCa通道可产生内皮超极化和血管舒张，这些作用可被IKCa通道抑制剂阻断。1-EBIO使内皮超极化，但不影响内皮[Ca 2 +]（i）。我们的结论是EDHF介导的脑动脉扩张的机制需要刺激内皮IKCa通道，以促进内皮超极化和随后的血管舒张。
The present study evaluated the role of endothelial intermediate conductance calcium-sensitive potassium channels (IKCa) in the mechanism of endothelium-derived hyperpolarizing factor ( EDHF)-mediated dilations in pressurized cerebral arteries. Male rat middle cerebral arteries (MCA) were mounted in an isolated vessel chamber, pressurized (85 mmHg), and luminally perfused (100 mul/min). Artery diameter was measured simultaneously with either endothelial intracellular Ca2+ concentration ([Ca2+](i); fura-2) or changes in endothelial membrane potential [4-{2-[6-(dioctylamino)-2-naphthalenyl] ethenyl} 1-(3-sulfopropyl)-pyridinium (di-8-ANEPPS)]. Nitric oxide synthase and cyclooxygenase inhibitors were present throughout. Luminal application of UTP produced EDHF-mediated dilations that correlated with significant endothelial hyperpolarization. The dilation and endothelial hyperpolarization were virtually abolished by inhibitors of IKCa channels but not by selective inhibitors of small or large conductance K-Ca channels ( apamin and iberiotoxin, respectively). Additionally, direct stimulation of endothelial IKCa channels with 1-ethyl-2-benzimidazolinone (1-EBIO) produced endothelial hyperpolarization and vasodilatation that were blocked by inhibitors of IKCa channels. 1- EBIO hyperpolarized the endothelium but did not affect endothelial [Ca2+](i). We conclude that the mechanism of EDHF-mediated dilations in cerebral arteries requires stimulation of endothelial IKCa channels to promote endothelial hyperpolarization and subsequent vasodilatation.