Schmidt Kjestine, de Wit Cor
Institut für Physiologie, Universität zu Lübeck, Lübeck, Germany.
Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) e.V. (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
Front Physiol. 2020 Dec 23;11:602930. doi: 10.3389/fphys.2020.602930. eCollection 2020.
The endothelium controls vascular tone adopting blood flow to tissue needs. It releases chemical mediators [e.g., nitric oxide (NO), prostaglandins (PG)] and exerts appreciable dilation through smooth muscle hyperpolarization, thus termed endothelium-dependent hyperpolarization (EDH). Initially, EDH was attributed to release of a factor, but later it was suggested that smooth muscle hyperpolarization might be derived from radial spread of an initial endothelial hyperpolarization through heterocellular channels coupling these vascular cells. The channels are indeed present and formed by connexins that enrich in gap junctions (GJ). data suggest that myoendothelial coupling underlies EDH-type dilations as evidenced by blocking experiments as well as simultaneous, merely identical membrane potential changes in endothelial and smooth muscle cells (SMCs), which is indicative of coupling through ohmic resistors. However, connexin-deficient animals do not display any attenuation of EDH-type dilations , and endothelial and SMCs exhibit distinct and barely superimposable membrane potential changes exerted by different means . Even if studied in the exact same artery EDH-type dilation exhibits distinct features and : in isometrically mounted vessels, it is rather weak and depends on myoendothelial coupling through connexin40 (Cx40), whereas as well as under isobaric conditions it is powerful and independent of myoendothelial coupling through Cx40. It is concluded that EDH-type dilations are distinct and a significant dependence on myoendothelial coupling does not reflect the situation under physiologic conditions . Myoendothelial coupling may act as a backup mechanism that is uncovered in the absence of the powerful EDH-type response and possibly reflects a situation in a pathophysiologic environment.
内皮细胞通过使血流适应组织需求来控制血管张力。它释放化学介质[如一氧化氮（NO）、前列腺素（PG）]，并通过平滑肌超极化产生明显的舒张作用，因此被称为内皮依赖性超极化（EDH）。最初，EDH被认为是由于一种因子的释放，但后来有人提出，平滑肌超极化可能源于最初的内皮超极化通过连接这些血管细胞的异细胞通道进行的径向扩散。这些通道确实存在，由富集于缝隙连接（GJ）中的连接蛋白形成。数据表明，肌内皮耦合是EDH型舒张的基础，阻断实验以及内皮细胞和平滑肌细胞（SMC）中同时出现的仅仅相同的膜电位变化证明了这一点，这表明是通过欧姆电阻进行耦合。然而，缺乏连接蛋白的动物并未表现出EDH型舒张有任何减弱，并且内皮细胞和SMC表现出由不同方式产生的明显且几乎不可叠加的膜电位变化。即使在完全相同的动脉中进行研究，EDH型舒张也表现出不同的特征：在等长安装的血管中，它相当微弱，并且依赖于通过连接蛋白40（Cx40）的肌内皮耦合，而在等压条件下它很强劲，并且不依赖于通过Cx40的肌内皮耦合。得出的结论是，EDH型舒张是不同的，对肌内皮耦合的显著依赖性并不能反映生理条件下的情况。肌内皮耦合可能作为一种备用机制，在缺乏强大的EDH型反应时被揭示出来，并且可能反映了病理生理环境中的一种情况。
