Griffith Tudor M, Chaytor Andrew T, Edwards David H
Department of Diagnostic Radiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Pharmacol Res. 2004 Jun;49(6):551-64. doi: 10.1016/j.phrs.2003.11.014.
Although an endothelium-derived hyperpolarizing factor (EDHF) has often been hypothesized to underpin vascular relaxations that are independent of nitric oxide (NO) and prostanoids, bioassay techniques have failed to confirm the existence of a freely transferable EDHF in a consistent fashion. Indeed, observations that inhibitors of direct cell-cell coupling such as connexin-mimetic peptides (e.g. Gap 26 and 27) and glycyrrhetinic acid derivatives attenuate "EDHF-type" smooth muscle hyperpolarizations and relaxations suggest that an electrotonic spread of endothelial hyperpolarization via myoendothelial and homocellular smooth muscle gap junctions plays an obligatory role in such responses. The endothelial hyperpolarization that initiates relaxation results from the opening of K(Ca) channels and is sustained by capacitative Ca(2+) entry triggered by the depletion of intracellular Ca(2+) stores in the endoplasmic reticulum. EDHF-type relaxations are also associated with a prostanoid-independent synthesis of cAMP that increases the conductance of gap junction channels and enhances the transmission of endothelial hyperpolarization through the vascular wall in a permissive fashion. This review will discuss the roles of these interacting signalling pathways in the mediation of the EDHF phenomenon.
尽管人们常常推测内皮源性超极化因子（EDHF）是介导不依赖于一氧化氮（NO）和前列腺素的血管舒张的基础，但生物测定技术一直未能以一致的方式证实可自由转移的EDHF的存在。事实上，诸如连接蛋白模拟肽（如Gap 26和27）和甘草次酸衍生物等直接细胞间偶联抑制剂可减弱“EDHF型”平滑肌超极化和舒张，这一观察结果表明，内皮超极化通过肌内皮和平滑肌细胞间缝隙连接进行电紧张性扩布在此类反应中起重要作用。引发舒张的内皮超极化是由钾钙通道开放引起的，并由内质网中细胞内钙库耗竭触发的钙池性钙内流维持。EDHF型舒张还与不依赖前列腺素的环磷酸腺苷（cAMP）合成有关，cAMP可增加缝隙连接通道的电导，并以允许的方式增强内皮超极化通过血管壁的传递。本综述将讨论这些相互作用的信号通路在介导EDHF现象中的作用。
