Vanheel B, Breyne J
Department of Physiology and Physiopathology, Gent University, U.Z.-Blok B, De Pintelaan 185, Ghent B-9000, Belgium.
Cardiovasc Res. 2004 Aug 1;63(2):331-7. doi: 10.1016/j.cardiores.2004.04.008.
In many blood vessels, stimulation of the endothelium with various vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin pathways, a third mechanism evoking dilatation. It is based on hyperpolarization of the vascular smooth muscle cell membrane. In the present study, we investigated the existence of endothelium-dependent hyperpolarization in small gastric arteries of the rat and explored its underlying mechanism.
Membrane potentials were recorded by conventional microelectrode techniques in isolated segments of small gastric arteries, the normalized diameter of which was determined from the passive wall tension-internal circumference characteristics as measured with a myograph.
After blocking NO and prostaglandin synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane hyperpolarization in endothelium intact but not in endothelium-denuded arteries. This membrane potential change was increased by pre-exposure to a low concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying potassium channels. Moreover, the acetylcholine-induced hyperpolarization was unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K-ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium-independent hyperpolarization after an initial peak depolarization.
We conclude that acetylcholine produces endothelium-dependent hyperpolarization in gastric small arteries, which does not rely on activation of smooth muscle cell inward rectifying K+ channels or Na/K pumps, and might prove to be another important regulator of gastric mucosal blood flow.
在许多血管中，除一氧化氮（NO）和前列环素途径外，用各种血管活性物质刺激内皮会诱导出第三种引起血管舒张的机制。它基于血管平滑肌细胞膜的超极化。在本研究中，我们调查了大鼠胃小动脉中内皮依赖性超极化的存在，并探讨了其潜在机制。
采用传统微电极技术记录离体胃小动脉段的膜电位，其归一化直径由用肌张力测定仪测量的被动壁张力 - 内周径特性确定。
在阻断NO和前列腺素合成后，应用乙酰胆碱（3×10⁻⁷ M）在内皮完整的动脉中导致膜超极化，而在内皮剥脱的动脉中则无此现象。预先暴露于低浓度（30 μM）的Ba²⁺可增加这种膜电位变化，Ba²⁺可选择性抑制内向整流钾通道。此外，乙酰胆碱诱导的超极化不受额外预先暴露于高浓度（0.5 mM）的钠钾ATP酶抑制剂哇巴因的影响，哇巴因本身在初始峰值去极化后会引起继发性缓慢的内皮非依赖性超极化。
我们得出结论，乙酰胆碱在胃小动脉中产生内皮依赖性超极化，其不依赖于平滑肌细胞内向整流钾通道或钠钾泵的激活，可能是胃黏膜血流的另一个重要调节因子。
