Félétou M, Vanhoutte P M
Département de Diabétologie, Institut de Recherches Servier, Suresnes, France.
J Physiol Pharmacol. 1999 Dec;50(4):525-34.
In response to various neurohumoral substances endothelial cells release nitric oxide (NO), prostacyclin and produce hyperpolarization of the underlying vascular smooth muscle cells, possibly by releasing another factor termed endothelium-derived hyperpolarizing factor (EDHF). EDHF-mediated responses are sensitive to the combination of two toxins, charybdotoxin plus apamin, but do not involve ATP-sensitive or large conductance calcium-activated potassium channels. As hyperpolarization of the endothelial cells is required in order to observe endothelium-dependent hyperpolarization, and electrical coupling through myo-endothelial gap junctions may explain the phenomenon. An alternative explanation is that the hyperpolarization of the endothelial cells causes an efflux of potassium that in turn activates the inwardly rectifying potassium conductance and the Na+/K+ pump of the smooth muscle cells. Endothelial cells produce metabolites of the cytochrome P450-monooxygenase that activate BKCa, and induce hyperpolarization of coronary arterial smooth muscle cells. The elucidation of the mechanism underlying endothelium-dependent hyperpolarization and the discovery of specific inhibitors of the phenomenon are prerequisite for the understanding of the physiological role of this alternative endothelial pathway involved in the control of vascular tone in health and disease.
作为对各种神经体液物质的反应，内皮细胞释放一氧化氮（NO）、前列环素，并可能通过释放另一种称为内皮衍生超极化因子（EDHF）的因子，使下层血管平滑肌细胞发生超极化。EDHF介导的反应对两种毒素（蝎毒素加蜂毒明肽）的组合敏感，但不涉及ATP敏感性或大电导钙激活钾通道。由于为了观察内皮依赖性超极化需要内皮细胞超极化，并且通过肌内皮间隙连接的电偶联可能解释这一现象。另一种解释是，内皮细胞的超极化导致钾外流，进而激活平滑肌细胞的内向整流钾电导和Na+/K+泵。内皮细胞产生细胞色素P450-单加氧酶的代谢产物，这些代谢产物激活大电导钙激活钾通道，并诱导冠状动脉平滑肌细胞超极化。阐明内皮依赖性超极化的潜在机制以及发现该现象的特异性抑制剂，是理解这一参与健康和疾病中血管张力控制的内皮替代途径生理作用的先决条件。
