Dong H, Jiang Y, Cole W C, Triggle C R
Smooth Muscle Research Group and Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1 Canada.
Br J Pharmacol. 2000 Aug;130(8):1983-91. doi: 10.1038/sj.bjp.0703474.
In the presence of L-NNA (100 microM), indomethacin (10 microM) and ODQ (10 microM), acetylcholine induced a concentration-dependent vasorelaxation of guinea-pig mesenteric and middle cerebral arteries precontracted with cirazoline or histamine, but not with high K(+), indicating the contribution of an endothelium-derived hyperpolarizing factor (EDHF). In cerebral arteries, charybdotoxin (ChTX; 0.1 microM) completely inhibited the indomethacin, L-NNA and ODQ-insensitive relaxation; iberiotoxin (IbTX, 0.1 microM), 4-aminopyridine (4-AP, 1 mM), or barium (30 microM) significantly reduced the response; in the mesenteric artery, ChTX and IbTX also reduced this relaxation. Glibenclamide (10 microM) had no affect in either the mesenteric or cerebral artery. Neither clotrimazole (1 microM) nor 7-ethoxyresorufin (3 microM) affected EDHF-mediated relaxation in the mesenteric artery, but abolished or attenuated EDHF-mediated relaxations in the cerebral artery. AM404 (30 microM), a selective anandamide transport inhibitor, did not affect the vasorelaxation response to acetylcholine in the cerebral artery, but in the mesenteric artery potentiated the vasorelaxation response to acetylcholine in an IbTX, and apamin-sensitive, but SR 141816A-insensitive manner. Ouabain (100 microM) almost abolished EDHF-mediated relaxation in the mesenteric artery, but enhanced the relaxation in the cerebral artery whereas the addition of K(+) (5 - 20 mM) to precontracted guinea-pig cerebral or mesenteric artery induced further vasoconstriction. These data suggest that in the guinea-pig mesenteric and cerebral arteries different EDHFs mediate acetylcholine-induced relaxation, however, EDHF is unlikely to be mediated by K(+).
在存在L - NNA（100微摩尔）、吲哚美辛（10微摩尔）和ODQ（10微摩尔）的情况下，乙酰胆碱可诱导预先用可乐定或组胺预收缩的豚鼠肠系膜动脉和大脑中动脉产生浓度依赖性血管舒张，但对高钾预收缩的血管无此作用，这表明存在内皮衍生超极化因子（EDHF）的作用。在大脑动脉中，大蝎毒素（ChTX；0.1微摩尔）完全抑制了吲哚美辛、L - NNA和ODQ不敏感的舒张反应；iberiotoxin（IbTX，0.1微摩尔）、4 - 氨基吡啶（4 - AP，1毫摩尔）或钡（30微摩尔）可显著降低该反应；在肠系膜动脉中，ChTX和IbTX也可降低这种舒张反应。格列本脲（10微摩尔）对肠系膜动脉和大脑动脉均无影响。克霉唑（1微摩尔）和7 - 乙氧基试卤灵（3微摩尔）均不影响肠系膜动脉中EDHF介导的舒张反应，但可消除或减弱大脑动脉中EDHF介导的舒张反应。AM404（30微摩尔），一种选择性花生四烯乙醇胺转运抑制剂，不影响大脑动脉中乙酰胆碱诱导的血管舒张反应，但在肠系膜动脉中，以IbTX和蜂毒明肽敏感但SR 141816A不敏感的方式增强了乙酰胆碱诱导的血管舒张反应。哇巴因（100微摩尔）几乎消除了肠系膜动脉中EDHF介导的舒张反应，但增强了大脑动脉中的舒张反应，而向预先收缩的豚鼠大脑或肠系膜动脉中添加钾离子（5 - 20毫摩尔）会诱导进一步的血管收缩。这些数据表明，在豚鼠肠系膜动脉和大脑动脉中，不同的EDHF介导乙酰胆碱诱导的舒张反应，然而，EDHF不太可能由钾离子介导。
