Ionic mechanisms involved in the flow- and pressure-sensor function of the endothelium.
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.
Rubanyi
G M
GM
Schering AG, Research Center, Institute of Pharmacology, Berlin, FRG.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D008955:Models, Cardiovascular; D009569:Nitric Oxide / Q000502:physiology; D011311:Pressoreceptors / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology*
D015220:Calcium Channels; D009569:Nitric Oxide; D000109:Acetylcholine; D002118:Calcium