K+ is an endothelium-derived hyperpolarizing factor in rat arteries
K+ is an endothelium-derived hyperpolarizing factor in rat arteries
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DOI：
10.1038/24388
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发表时间：
1998-11-19
期刊：
影响因子：
64.8
通讯作者：
Weston, AH
中科院分区：
文献类型：
--
作者：
Edwards, G;Dora, KA;Weston, AH
在动脉中，乙酰胆碱等毒蕈碱激动剂会释放一种不明的内皮源性超极化因子 (EDHF)，该因子既不是前列环素，也不是一氧化氮 (1-3)。在这里，我们发现哇巴因加 Ba2+ 可抑制 EDHF 诱导的平滑肌超极化和小阻力动脉舒张；哇巴因是 Na+/K+ ATP 酶 (4) 的阻断剂，而 Ba2+ 则阻断内向整流 K+ 通道 (5)。细胞外 K+ 量的小幅增加以哇巴因和 Ba2+ 敏感但不依赖于内皮的方式模拟 EDHF 的这些作用。乙酰胆碱使内皮细胞超极化并增加肌内皮空间中的 K+ 浓度； Charybdotoxin 加 apamin 可以消除这些作用。这种毒素组合也消除了 EDHF 引起的平滑肌超极化，但这些毒素不影响添加 K+ 引起的平滑肌超极化。这些数据表明，EDHF 是 K+，通过内皮细胞上的 Charybdotoxin 和 apamin 敏感的 K+ 通道流出。由此产生的肌内皮 K+ 浓度增加，通过激活 Ba2+ 敏感 K+ 通道和 Na+/K+ ATP 酶，使邻近的平滑肌细胞超极化和松弛。这些结果表明，源自血管本身的 K+ 水平波动对于调节哺乳动物的血压和血流非常重要。
In arteries, muscarinic agonists such as acetylcholine release an unidentified, endothelium-derived hyperpolarizing factor (EDHF) which is neither prostacyclin nor nitric oxide(1-3). Here we show that EDHF-induced hyperpolarization of smooth muscle and relaxation of small resistance arteries are inhibited by ouabain plus Ba2+; ouabain is a blocker of Na+/K+ ATPase(4) and Ba2+ blocks inwardly rectifying K+ channels(5). Small increases in the amount of extracellular K+ mimic these effects of EDHF in a ouabain- and Ba2+-sensitive, but endothelium-independent, manner. Acetylcholine hyperpolarizes endothelial tells and increases the K+ concentration in the myoendothelial space; these effects are abolished by charybdotoxin plus apamin. Hyperpolarization of smooth muscle by EDHF is also abolished by this toxin combination, but these toxins do not affect the hyperpolarization of smooth muscle by added K+. These data show that EDHF is K+ that effluxes through charybdotoxin- and apamin-sensitive K+ channels on endothelial cells. The resulting increase in myoendothelial K+ concentration hyperpolarizes and relaxes adjacent smooth-muscle cells by activating Ba2+-sensitive K+ channels and Na+/K+ ATPase, These results show that fluctuations in K+ levels originating within the blood vessel itself are important in regulating mammalian blood pressure and flow.