TEA inhibits ACh-induced EDRF release: endothelial Ca(2+)-dependent K+ channels contribute to vascular tone.
TEA inhibits ACh-induced EDRF release: endothelial Ca(2+)-dependent K+ channels contribute to vascular tone.
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TEA 抑制 ACh 诱导的 EDRF 释放：内皮 Ca(2) 依赖性 K 通道有助于血管张力。
DOI：
10.1152/ajpheart.1994.267.3.h1135
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
vanBreemen,C
中科院分区：
文献类型：
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作者：
Demirel,E;Rusko,J;Laskey,RE;Adams,DJ;vanBreemen,C
用生物测定法、荧光分光光度法和膜片钳技术分别研究了K(+)通道阻断剂对乙酰胆碱(ACh)引起的血管平滑肌松弛、血管内皮细胞内游离钙浓度([Ca~(2+)]i)升高和ACh诱发的血管内皮细胞外向钾电流的影响。在生物测定实验中，当ACh通过内皮完整的供体血管段灌流时，ACh以浓度依赖的方式引起内皮剥离的主动脉环松弛，但当直接灌流到受体主动脉环上时，ACh不能引起血管环的松弛。ACh诱导的松弛可被通过供体灌流的四乙基铵离子(TEA；5 mM)抑制，但不能直接灌流到受体节段。在上述两种情况下，格列本脲对ACh诱导的生物测定环的松弛均无影响。ACh使主动脉条内皮细胞表面[Ca~(2+)]i升高，但对外膜表面无明显影响。TEA可抑制ACh诱导的[Ca~(2+)]i升高，而格列本脲对此无影响。在新鲜分离内皮细胞的膜片钳实验中，ACh诱发一种双相外向电流，该电流可被TEA(3 MM)完全消除。结论：钙依赖的K+通道在激动剂刺激下升高[Ca~(2+)]i，从而促进内皮源性松弛因子(EDRF)的合成/释放。此外，内皮细胞对ATP敏感的K+通道不参与ACh引起的血管松弛或引起兔胸主动脉内皮细胞[Ca~(2+)]i的升高。
The effects of K(+)-channel blockers on the acetylcholine (ACh)-induced relaxation of vascular smooth muscle, intracellular free Ca2+ concentration ([Ca2+]i) elevation, and ACh-evoked outward K+ current of endothelial cells of rabbit aorta were studied using bioassay, spectrofluorimetry, and patch-clamp techniques, respectively. In bioassay experiments, ACh caused relaxation of endothelium-denuded aortic rings in a concentration-dependent manner when perfused through an endothelium-intact donor segment of aorta but not when perfused directly onto the recipient aortic ring. ACh-induced relaxation was inhibited by perfusion of tetraethylammonium ions (TEA; 5 mM) through the donor but not by perfusion directly onto the recipient segment. Glibenclamide had no effect on ACh-induced relaxation of the bioassay ring in either situation. ACh increased [Ca2+]i at the endothelial surface of aortic strips but not at the adventitial surface. TEA inhibited ACh-induced [Ca2+]i elevation, whereas glibenclamide had no effect. In patch-clamp experiments with freshly isolated endothelial cells, ACh evoked a biphasic outward current which was completely abolished by TEA (3 mM). It is concluded that Ca(2+)-dependent K+ channels are important for increasing [Ca2+]i during agonist stimulation and consequently for the synthesis/release of endothelium-derived relaxing factors (EDRFs). Furthermore, endothelial ATP-sensitive K+ channels do not contribute to ACh-induced relaxation or evoke an increase in endothelial [Ca2+]i of rabbit thoracic aorta.