Busse R, Pohl U, Lückhoff A
Department of Applied Physiology, University of Freiburg, FRG.
Z Kardiol. 1989;78 Suppl 6:64-9.
The endothelium plays an important role in the control of vascular tone and platelet activity. This is mainly achieved by the release of autacoids, particularly EDRF (identical with nitric oxide, NO) and PGI2. The release of both autacoids is evoked by physical factors like hypoxia and shear stress and by various chemical compounds like acetylcholine, ATP and bradykinin. These agonists bind to membrane receptors coupled to phospholipase C, thereby increasing production of inositol-1,4,5-trisphosphate (IP3). IP3 mobilizes Ca2+ from intracellular stores, thus elevating the intracellular free calcium concentration ([Ca2+]i), in synergy with a simultaneously induced transmembrane Ca2+ influx. The level of [Ca2+]i closely correlates with endothelial production of PGI2 whereas Ca2+ influx is apparently a decisive signal for the sustained release of EDRF. This influx may be facilitated by an agonist-induced membrane hyperpolarization probably being mediated by activation of Ca2+-dependent K+ channels. Depolarization of the endothelial cell membrane on the other hand (evoked by raising the extracellular K+ concentration) attenuates the Ca2+ influx as well as EDRF release. The agonist-induced endothelial hyperpolarization may also be electrotonically transmitted to adjacent smooth muscle cells via myoendothelial gap junctions and may act synergistically with the EDRF-mediated relaxation. Alternatively, spread of this electrical signal along the endothelial lining may enhance the release of autacoids.
内皮细胞在控制血管张力和血小板活性方面发挥着重要作用。这主要是通过自分泌物质的释放来实现的，特别是内皮舒张因子（与一氧化氮，即NO相同）和前列环素（PGI2）。这两种自分泌物质的释放是由缺氧和剪切应力等物理因素以及乙酰胆碱、ATP和缓激肽等各种化合物引发的。这些激动剂与偶联磷脂酶C的膜受体结合，从而增加肌醇-1,4,5-三磷酸（IP3）的产生。IP3从细胞内储存库中动员Ca2+，从而提高细胞内游离钙浓度（[Ca2+]i），与同时诱导的跨膜Ca2+内流协同作用。[Ca2+]i的水平与内皮细胞PGI2的产生密切相关，而Ca2+内流显然是内皮舒张因子持续释放的决定性信号。这种内流可能因激动剂诱导的膜超极化而促进，膜超极化可能由钙依赖性钾通道的激活介导。另一方面，内皮细胞膜的去极化（通过提高细胞外K+浓度引起）会减弱Ca2+内流以及内皮舒张因子的释放。激动剂诱导的内皮超极化也可能通过肌内皮间隙连接以电紧张方式传递到相邻的平滑肌细胞，并可能与内皮舒张因子介导的舒张协同作用。或者，这种电信号沿内皮衬里的传播可能会增强自分泌物质的释放。
