豚鼠颈动脉中的环氧二十碳三烯酸、钾通道阻滞剂与内皮依赖性超极化

Epoxyeicosatrienoic acids, potassium channel blockers and endothelium-dependent hyperpolarization in the guinea-pig carotid artery.

作者信息

Chataigneau T, Félétou M, Duhault J, Vanhoutte P M

机构信息

Département de Diabétologie, Institut de Recherches Servier, Suresnes, France.

出版信息

Br J Pharmacol. 1998 Feb;123(3):574-80. doi: 10.1038/sj.bjp.0701629.

DOI:10.1038/sj.bjp.0701629

PMID:9504399

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565190/

Abstract

Using intracellular microelectrodes, we investigated the effects of 17-octadecynoic acid (17-ODYA) on the endothelium-dependent hyperpolarization induced by acetylcholine in the guinea-pig isolated internal carotid artery with endothelium. 2. In the presence of Nomega-nitro-L-arginine (L-NOARG, 100 microM) and indomethacin (5 microM) to inhibit nitric oxide synthase and cyclo-oxygenase, acetylcholine (1 microM) evoked an endothelium-dependent hyperpolarization which averaged -16.4 mV starting from a resting membrane potential of -56.8 mV. There was a negative correlation between the amplitude of the hyperpolarization and the absolute values of the resting membrane potential. 3. The acetylcholine-induced endothelium-dependent hyperpolarization was not altered by charybdotoxin (0.1 microM) or iberiotoxin (30 nM). It was partially but significantly reduced by apamin (0.5 microM) to -12.8+/-1.2 mV (n=10) or the combination of apamin plus iberiotoxin (-14.3+/-3.4mV, n=4). However, the combination of charybdotoxin and apamin abolished the hyperpolarization and under these conditions, acetylcholine evoked a depolarization (+ 7.1+/-3.7 mV, n = 8). 4. 17-ODYA (10 microM) produced a significant hyperpolarization of the resting membrane potential which averaged -59.6 mV and a partial but significant inhibition of the acetylcholine-induced endothelium-dependent hyperpolarization (-10.9 mV). 5. Apamin did not modify the effects of 17-ODYA but in the presence of charybdotoxin or iberiotoxin, 17-ODYA no longer influenced the resting membrane potential or the acetylcholine-induced hyperpolarization. 6. When compared to solvent (ethanol, 1% v/v), epoxyeicosatrienoic acids (EpETrEs) (5,6-, 8,9-, 11,12- and 14,15-EpETrE, 3 microM) did not affect the cell membrane potential and did not relax the guinea-pig isolated internal carotid artery. 7. These results indicate that, in the guinea-pig internal carotid artery, the involvement of metabolites of arachidonic acid through the cytochrome P450 pathway in endothelium-dependent hyperpolarization is unlikely. Furthermore, the hyperpolarization mediated by the endothelium-derived hyperpolarizing factor (EDHF) is probably not due to the opening of BK(Ca) channels.

摘要

我们使用细胞内微电极，研究了17-十八碳炔酸（17-ODYA）对豚鼠离体带内皮的颈内动脉中乙酰胆碱诱导的内皮依赖性超极化的影响。2. 在存在Nω-硝基-L-精氨酸（L-NOARG，100μM）和吲哚美辛（5μM）以抑制一氧化氮合酶和环氧化酶的情况下，乙酰胆碱（1μM）诱发了内皮依赖性超极化，从静息膜电位-56.8 mV开始，平均为-16.4 mV。超极化幅度与静息膜电位绝对值之间呈负相关。3. 乙酰胆碱诱导的内皮依赖性超极化不受卡律蝎毒素（0.1μM）或埃博毒素（30 nM）的影响。蜂毒明肽（0.5μM）可使其部分但显著降低至-12.8±1.2 mV（n = 10），或蜂毒明肽与埃博毒素联合使用时降低至-14.3±3.4 mV（n = 4）。然而，卡律蝎毒素和蜂毒明肽联合使用可消除超极化，在这些条件下，乙酰胆碱诱发去极化（+7.1±3.7 mV，n = 8）。4. 17-ODYA（10μM）使静息膜电位产生显著超极化，平均为-59.6 mV，并对乙酰胆碱诱导的内皮依赖性超极化产生部分但显著的抑制作用（-10.9 mV）。5. 蜂毒明肽不改变17-ODYA的作用，但在存在卡律蝎毒素或埃博毒素的情况下，17-ODYA不再影响静息膜电位或乙酰胆碱诱导的超极化。6. 与溶剂（乙醇，1% v/v）相比，环氧二十碳三烯酸（EpETrEs）（5,6-、8,9-、11,12-和14,15-EpETrE，3μM）不影响细胞膜电位，也不使豚鼠离体颈内动脉舒张。7. 这些结果表明，在豚鼠颈内动脉中，花生四烯酸通过细胞色素P450途径的代谢产物不太可能参与内皮依赖性超极化。此外，内皮源性超极化因子（EDHF）介导的超极化可能不是由于大电导钙激活钾通道（BK(Ca)通道）的开放所致。