Rubanyi G M
Schering AG, Research Center, Institute of Pharmacology, Berlin, FRG.
Z Kardiol. 1991;80 Suppl 7:91-4.
Changes in hemodynamic forces (shear stress and pressure) modulate the tone of blood vessels. Recent evidence suggests that the endothelium plays an important role in these responses. Cascade bioassay experiments with various blood vessels demonstrated that increases in shear stress stimulated, and elevated transmural pressure suppressed the synthesis/release of endothelium-derived relaxing factor (EDRF). Studying the potential mechanisms of stimulus-response coupling in endothelial cells, it was shown that shear stress hyperpolarizes and pressure depolarizes the membrane of endothelial cells. Using whole-cell patch-clamping and various inhibitors of ion channels, it was demonstrated that modulation of the inward rectifying K(+)-channel may be the initial step in stimulus-response coupling: shear stress activates and pressure inactivates this channel, respectively. Since membrane potential is the main determinant of Ca(2+)-entry into endothelial cells, this still hypothetical mechanism may explain the opposing effects of shear stress (increased Ca(2+)-entry) and pressure (decreased Ca(2+)-entry) on the synthesis/release of EDRF.
血流动力学力（切应力和压力）的变化可调节血管张力。最近的证据表明，内皮在这些反应中起重要作用。对各种血管进行的级联生物测定实验表明，切应力增加会刺激内皮衍生舒张因子（EDRF）的合成/释放，而跨壁压力升高则会抑制其合成/释放。在研究内皮细胞中刺激-反应偶联的潜在机制时发现，切应力使内皮细胞膜超极化，而压力使其去极化。使用全细胞膜片钳技术和各种离子通道抑制剂，证明内向整流钾通道的调节可能是刺激-反应偶联的初始步骤：切应力分别激活该通道，而压力使其失活。由于膜电位是钙离子进入内皮细胞的主要决定因素，这种仍属假设的机制可能解释切应力（增加钙离子内流）和压力（减少钙离子内流）对EDRF合成/释放的相反作用。
