Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Curr Top Membr. 2020;85:327-355. doi: 10.1016/bs.ctm.2020.01.004. Epub 2020 Mar 6.
The endothelium is an important regulator of arterial vascular tone, acting to release nitric oxide (NO) and open Ca-activated K (K) channels to relax vascular smooth muscle cells (VSMCs). While agonists acting at endothelial cell (EC) receptors are widely used to assess the ability of the endothelium to reduce vascular tone, the intrinsic EC-dependent mechanisms are less well characterized. In small resistance arteries and arterioles, the presence of heterocellular gap junctions termed myoendothelial gap junctions (MEGJs) allows the passage of not only current, but small molecules including Ca and inositol trisphosphate (IP). When stimulated to contract, the increase in VSM Ca and IP can therefore potentially pass through MEGJs to activate adjacent ECs. This activation releases NO and opens K channels, which act to limit contraction. This myoendothelial feedback (MEF) is amplified by EC Ca influx and release pathways, and is dynamically modulated by processes regulating gap junction conductance. There is a remarkable localization of key signaling and regulatory proteins within the EC projection toward VSM, and the intrinsic EC-dependent signaling pathways occurring with this highly specialized microdomain are reviewed.
内皮细胞是动脉血管张力的重要调节者，它通过释放一氧化氮（NO）和打开 Ca 激活的 K（K）通道来松弛血管平滑肌细胞（VSMCs）。虽然作用于内皮细胞（EC）受体的激动剂被广泛用于评估内皮细胞降低血管张力的能力，但内皮细胞内在的、依赖于自身的机制尚未得到很好的描述。在小阻力血管和小动脉中，存在称为肌内皮缝隙连接（MEGJ）的异细胞缝隙连接，允许不仅电流，而且包括 Ca 和三磷酸肌醇（IP）在内的小分子通过。当 VSM 被刺激收缩时，Ca 和 IP 的增加因此可能通过 MEGJ 传递以激活相邻的 EC。这种激活释放了 NO 和打开了 K 通道，从而限制了收缩。这种肌内皮反馈（MEF）被 EC Ca 内流和释放途径放大，并通过调节缝隙连接电导的过程进行动态调节。在 EC 向 VSM 的投射中，存在着关键信号转导和调节蛋白的显著定位，并且在这个高度特化的微域中发生的内在 EC 依赖的信号转导途径也进行了综述。
