Ding H, Triggle C R
Department of Pharmacology and Therapeutics and the Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
J Pharmacol Toxicol Methods. 2000 Sep-Oct;44(2):441-52. doi: 10.1016/s1056-8719(00)00127-1.
Nitric oxide (NO), together with prostacyclin (PGI2), mediates shear stress and endothelium-dependent vasodilator-mediated vasorelaxation. In the presence of inhibition of NO synthase (NOS) with nitroarginine analogues, such as of N(w)-nitro-L-arginine methyl ester (L-NAME) and N(w)-nitro-L-arginine (L-NNA), and indomethacin, to inhibit cyclooxygenase (COX) and the synthesis of PGI2, many blood vessels still respond with an endothelium-dependent relaxation to either chemical [i.e. acetylcholine (ACh)] or mechanical (shear stress) activation. This non-NO and non-PGI2 vasorelaxation appears to be mediated by hyperpolarization of the vascular smooth muscle cell (VSMC). Although NO can hyperpolarize VSMC, a novel mediator, the endothelium-derived hyperpolarizing factor (EDHF), which opens a VSMC K(+) channel(s) notably in resistance vessels, has been proposed. Little agreement exists as to the nature of this putative factor, but several candidate molecules have been proposed and evidence, notably from the microcirculation, suggests that endothelium-dependent hyperpolarization (EDH) may be mediated via low electrical resistance coupling via myoendothelial gap junctions. We describe a number of techniques that are being used to identify EDHF and present data that address the contribution of a small increase in extracellular K(+) as an EDHF.
一氧化氮（NO）与前列环素（PGI2）共同介导剪切应力和内皮依赖性血管舒张剂介导的血管舒张。在用硝基精氨酸类似物如N（ω）-硝基-L-精氨酸甲酯（L-NAME）和N（ω）-硝基-L-精氨酸（L-NNA）抑制一氧化氮合酶（NOS），以及用吲哚美辛抑制环氧化酶（COX）和PGI2合成的情况下，许多血管对化学物质[即乙酰胆碱（ACh）]或机械（剪切应力）激活仍会产生内皮依赖性舒张反应。这种非NO和非PGI2介导的血管舒张似乎是由血管平滑肌细胞（VSMC）的超极化介导的。尽管NO可以使VSMC超极化，但有人提出了一种新的介质，即内皮衍生的超极化因子（EDHF），它在阻力血管中特别能打开VSMC的钾通道。关于这种假定因子的性质，目前还没有达成共识，但已经提出了几种候选分子，并且有证据表明，尤其是来自微循环的证据表明，内皮依赖性超极化（EDH）可能是通过肌内皮间隙连接的低电阻耦合介导的。我们描述了一些用于识别EDHF的技术，并展示了一些数据，这些数据探讨了细胞外钾离子少量增加作为一种EDHF的作用。
