Bény J L, Schaad O
Department of Zoology and Animal Biology, University of Geneva Sciences III, Quai E.-Ansermet 30, CH-1211 Geneva 4, Switzerland.
Br J Pharmacol. 2000 Nov;131(5):965-73. doi: 10.1038/sj.bjp.0703658.
In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth muscles by gating inward rectified potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteries. On coronary strips, the inhibition of calcium-dependent potassium channels with 100 nM apamin plus 100 microM charibdotoxin inhibited the endothelium-dependent relaxations, produced by 10 nM substance P and 300 nM bradykinin and resistant to nitro-L-arginine and indomethacin. The scavenging of potassium with 2 mM Kryptofix 2.2.2 abolished the endothelium-dependent relaxations produced by the kinins and resistant to nitro-L-arginine and indomethacin. Forty microM 18alpha glycyrrethinic acid or 50 microM palmitoleic acid, both uncoupling agents, did not inhibit these kinin relaxations. Therefore, EDHF does not result from an electrotonic spreading of an endothelial hyperpolarization. Barium (0.3 nM) did not inhibit the kinin relaxations resistant to nitro-L-arginine and indomethacin. Therefore, EDHF does not result from the activation of inward rectified potassium channels. Five hundred nM ouabain abolished the endothelium-dependent relaxations resistant to nitro-L-arginine and indomethacin without inhibiting the endothelium-derived NO relaxation. The perifusion of a medium supplemented with potassium depolarized and contracted a coronary strip; however, the short application of potassium hyperpolarized the smooth muscles. These results are compatible with the concept that, in porcine coronary artery, the EDHF is potassium released by the endothelial cells and that this ion hyperpolarizes and relaxes the smooth muscles by activating the Na(+)-K(+)ATPase.
在大鼠肝动脉中，内皮源性超极化因子（EDHF）被确定为钾离子。钾离子通过内向整流钾通道的门控以及激活钠钾三磷酸腺苷酶（Na(+)-K(+)ATPase）使平滑肌超极化。我们的目标是研究钾离子是否能解释猪冠状动脉中的EDHF。在冠状动脉条上，用100 nM蜂毒明肽加100 μM查里毒素抑制钙依赖性钾通道，可抑制由10 nM P物质和300 nM缓激肽引起的内皮依赖性舒张，且这种舒张对硝基-L-精氨酸和吲哚美辛具有抗性。用2 mM穴状配体2.2.2清除钾离子可消除由激肽引起的、对硝基-L-精氨酸和吲哚美辛具有抗性的内皮依赖性舒张。40 μM 18α-甘草次酸或50 μM棕榈油酸这两种解偶联剂均不抑制这些激肽舒张。因此，EDHF并非由内皮超极化的电紧张性扩布所致。0.3 nM钡离子不抑制对硝基-L-精氨酸和吲哚美辛具有抗性的激肽舒张。因此，EDHF并非由内向整流钾通道的激活所致。500 nM哇巴因消除了对硝基-L-精氨酸和吲哚美辛具有抗性的内皮依赖性舒张，但不抑制内皮源性一氧化氮介导的舒张。用补充了钾离子的培养基进行灌流可使冠状动脉条去极化并收缩；然而，短暂施加钾离子可使平滑肌超极化。这些结果与以下概念相符：在猪冠状动脉中，EDHF是内皮细胞释放的钾离子，且该离子通过激活Na(+)-K(+)ATPase使平滑肌超极化并舒张。
