Department of Pharmacology and Pharmacy, University of Hong Kong, China.
Acta Pharmacol Sin. 2010 Sep;31(9):1095-102. doi: 10.1038/aps.2010.127. Epub 2010 Aug 16.
Endothelial cells release various substances to control the tone of the underlying vascular smooth muscle. Nitric oxide (NO) is the best defined endothelium-derived relaxing factor (EDRF). Endothelial cells can also increase vascular tone by releasing endothelium-derived contracting factors (EDCF). The over-production of EDCF contributes to the endothelial dysfunctions which accompanies various vascular diseases. The present review summarizes and discusses the mechanisms leading to the release of EDCFs derived from the metabolism of arachidonic acid. This release can be triggered by agonists such as acetylcholine, adenosine nucleotides or by stretch. All these stimuli are able to induce calcium influx into the endothelial cells, an effect which can be mimicked by calcium ionophores. The augmentation in intracellular calcium ion concentration initiates the release of EDCF. Downstream processes include activation of phospholipase A(2) (PLA(2)), cyclooxygenases (COX) and the production of reactive oxygen species (ROS) and vasoconstrictor prostanoids (endoperoxides, prostacyclin, thromboxane A(2) and other prostaglandins) which subsequently diffuse to, and activate thromboxane-prostanoid (TP) receptors on the vascular smooth muscle cells leading to contraction.
内皮细胞释放各种物质来控制其下的血管平滑肌的张力。一氧化氮（NO）是最明确的内皮衍生舒张因子（EDRF）。内皮细胞也可以通过释放内皮衍生收缩因子（EDCF）来增加血管张力。EDCF 的过度产生导致伴随各种血管疾病的内皮功能障碍。本综述总结和讨论了导致源自花生四烯酸代谢的 EDCF 释放的机制。这种释放可以被激动剂如乙酰胆碱、腺苷核苷酸或张力触发。所有这些刺激都能够诱导内皮细胞内钙离子内流，钙离子载体可以模拟这种作用。细胞内钙离子浓度的增加引发了 EDCF 的释放。下游过程包括激活磷脂酶 A2（PLA2）、环氧化酶（COX）以及产生活性氧物质（ROS）和血管收缩性前列腺素（过氧化物、前列环素、血栓烷 A2 和其他前列腺素），随后扩散到血管平滑肌细胞并激活血栓烷-前列腺素（TP）受体，导致收缩。
