内皮衍生超极化因子和钾离子通过不同机制诱导人皮下阻力动脉舒张。
Endothelium-derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries.
作者信息
McIntyre C A, Buckley C H, Jones G C, Sandeep T C, Andrews R C, Elliott A I, Gray G A, Williams B C, McKnight J A, Walker B R, Hadoke P W
机构信息
Department of Medical Sciences, Western General Hospital, University of Edinburgh, Edinburgh.
出版信息
Br J Pharmacol. 2001 Jul;133(6):902-8. doi: 10.1038/sj.bjp.0704143.
This investigation examined the hypothesis that release of K(+) accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12 microm, n=48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) - 3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA; 0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were attenuated (P<0.0001) by removal of the endothelium (E(max) 8.21+/-5.39% and 11.56+/-8.49%, respectively; n=6 - 7). Indomethacin (10 microM) did not alter ACh-induced relaxation whereas L-NOARG (100 microM) reduced this response (E(max) 61.7+/-3.4%, P<0.0001; n=6). The combination of ChTx (50 nM) and apamin (30 nM) attenuated the L-NOARG-insensitive component of ACh-induced relaxation (E(max): 15.2+/-10.5%, P<0.002, n=6) although these arteries retained the ability to relax in response to 100 microM SIN-1 (E(max) 127.6+/-13.0%, n=3). Exposure to BaCl(2) (30 microM) and Ouabain (1 mM) did not attenuate the L-NOARG resistant component of ACh-mediated relaxation (E(max), 76.09+/-8.92, P=0.16; n=5). KCl-mediated relaxation was unaffected by L-NOARG+indomethacin (E(max); 68.1+/-5.6%, P=0.33; n=5) or the combination of L-NOARG/indomethacin/ChTx/apamin (E(max); 86.61+/-14.02%, P=0.35; n=6). In contrast, the combination of L-NOARG, indomethacin, ouabain and BaCl(2) abolished this response (E(max), 5.67+/-2.59%, P<0.0001, n=6). The characteristics of KCl-mediated relaxation differed from those of the nitric oxide/prostaglandin-independent component of the response to ACh, and were endothelium-dependent, indicating that K(+) does not act as an EDHF in human subcutaneous resistance arteries.
本研究通过比较乙酰胆碱（ACh）和氯化钾（KCl）在人皮下阻力动脉中产生的舒张反应，检验了钾离子（K⁺）释放介导内皮依赖性超极化因子（EDHF）活性的假说。取自人皮下脂肪活检的阻力动脉（内径244±12微米，n = 48）悬挂于线肌张力测定仪中。在用去甲肾上腺素（NA；0.1 - 3微摩尔）收缩后，获得ACh（10⁻⁹ - 3×10⁻⁵摩尔）和KCl（2.5 - 25毫摩尔）的累积浓度 - 反应曲线。ACh（最大效应值[E(max)]99.07±9.61%；半数抑制浓度的负对数[-LogIC(50)]7.03±0.22；n = 9）和KCl（E(max)74.14±5.61%；-LogIC(50)2.12±0.07；n = 10）诱导的舒张反应在去除内皮后减弱（P<0.0001）（E(max)分别为8.21±5.39%和11.56±8.49%；n = 6 - 7）。吲哚美辛（10微摩尔）不改变ACh诱导的舒张反应，而L - 硝基精氨酸（L - NOARG，100微摩尔）降低此反应（E(max)61.7±3.4%，P<0.0001；n = 6）。ChTx（50纳摩尔）和蜂毒明肽（30纳摩尔）的组合减弱了ACh诱导舒张反应中对L - NOARG不敏感的成分（E(max)：15.2±10.5%，P<0.002，n = 6），尽管这些动脉对100微摩尔SIN - 1仍有舒张能力（E(max)127.6±13.0%，n = 3）。暴露于氯化钡（BaCl₂，30微摩尔）和哇巴因（1毫摩尔）并不减弱ACh介导舒张反应中对L - NOARG耐药的成分（E(max)，76.09±8.92，P = 0.16；n = 5）。KCl介导的舒张反应不受L - NOARG + 吲哚美辛（E(max)；68.1±5.6%，P = 0.33；n = 5）或L - NOARG/吲哚美辛/ChTx/蜂毒明肽组合（E(max)；86.61±14.02%，P = 0.35；n = 6）的影响。相反，L - NOARG、吲哚美辛、哇巴因和氯化钡的组合消除了此反应（E(max)，5.67±2.59%，P<0.0001，n = 6）。KCl介导的舒张反应特征不同于ACh反应中一氧化氮/前列腺素非依赖性成分的特征，且是内皮依赖性的，表明K⁺在人皮下阻力动脉中并非作为EDHF起作用。
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