Department of Anesthesiology and Pain Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si 52727, Republic of Korea.
Institute of Health Sciences, Gyeongsang National University, Jinju-si 52727, Republic of Korea.
Int J Mol Sci. 2018 Jun 26;19(7):1876. doi: 10.3390/ijms19071876.
The goal of this study was to investigate the effect of lipid emulsion on a toxic dose of local anesthetic-mediated reduction of vasodilation evoked by the ATP-sensitive potassium (K) channel agonist levcromakalim. The effect of lipid emulsion (LE) and linoleic acid on the local anesthetic-mediated reduction of vasodilation and membrane hyperpolarization evoked by levcromakalim was assessed in isolated endothelium-denuded vessels (rat aorta and mesenteric artery) and aortic vascular smooth muscle cells. The effect of LE and linoleic acid on K channel activity in transfected HEK-293 cells was investigated, as was the effect of LE on bupivacaine concentration. The efficacy of LE in attenuating the local anesthetic-mediated reduction of vasodilation evoked by levcromakalim was correlated with the lipid solubility of the local anesthetic. Linoleic acid attenuated the bupivacaine-mediated reduction of vasodilation evoked by levcromakalim. LE decreased the bupivacaine-mediated reduction of membrane hyperpolarization evoked by levcromakalim but did not significantly alter the mepivacaine-mediated reduction. LE and linoleic acid both reversed the bupivacaine-mediated decrease of K activity and enhanced K activity. LE decreased the bupivacaine concentration. Linoleic acid may be the major contributor to LE-induced attenuation of bupivacaine-mediated reduction of vasodilation evoked by levcromakalim via the direct activation of K channels and indirect effects.
本研究旨在探讨脂质乳剂对局部麻醉剂介导的三磷酸腺苷敏感性钾 (K) 通道激动剂左卡尼汀引起的血管舒张抑制作用的影响。在分离的去内皮血管（大鼠主动脉和肠系膜动脉）和主动脉血管平滑肌细胞中，评估了脂质乳剂 (LE) 和亚油酸对左卡尼汀介导的血管舒张和膜超极化抑制的影响。研究了 LE 和亚油酸对转染的 HEK-293 细胞中 K 通道活性的影响，以及 LE 对布比卡因浓度的影响。LE 减轻左卡尼汀介导的布比卡因引起的血管舒张抑制的效果与局部麻醉剂的脂溶性相关。亚油酸减弱了布比卡因介导的左卡尼汀引起的血管舒张抑制。LE 降低了布比卡因介导的左卡尼汀引起的膜超极化抑制，但对甲哌卡因介导的抑制没有显著影响。LE 和亚油酸均逆转了布比卡因介导的 K 活性降低，并增强了 K 活性。LE 降低了布比卡因浓度。亚油酸可能是 LE 诱导的左卡尼汀介导的布比卡因引起的血管舒张抑制减弱的主要原因，这是通过直接激活 K 通道和间接作用实现的。
