Mechanisms controlling the production of endothelial autacoids.
The endothelium plays an important role in the control of vascular tone and platelet activity. This is mainly achieved by the release of autacoids, particularly EDRF (identical with nitric oxide, NO) and PGI2. The release of both autacoids is evoked by physical factors like hypoxia and shear stress and by various chemical compounds like acetylcholine, ATP and bradykinin. These agonists bind to membrane receptors coupled to phospholipase C, thereby increasing production of inositol-1,4,5-trisphosphate (IP3). IP3 mobilizes Ca2+ from intracellular stores, thus elevating the intracellular free calcium concentration ([Ca2+]i), in synergy with a simultaneously induced transmembrane Ca2+ influx. The level of [Ca2+]i closely correlates with endothelial production of PGI2 whereas Ca2+ influx is apparently a decisive signal for the sustained release of EDRF. This influx may be facilitated by an agonist-induced membrane hyperpolarization probably being mediated by activation of Ca2+-dependent K+ channels. Depolarization of the endothelial cell membrane on the other hand (evoked by raising the extracellular K+ concentration) attenuates the Ca2+ influx as well as EDRF release. The agonist-induced endothelial hyperpolarization may also be electrotonically transmitted to adjacent smooth muscle cells via myoendothelial gap junctions and may act synergistically with the EDRF-mediated relaxation. Alternatively, spread of this electrical signal along the endothelial lining may enhance the release of autacoids.
Busse
R
R
Department of Applied Physiology, University of Freiburg, FRG.
Pohl
U
U
Lückhoff
A
A
D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*
D009569:Nitric Oxide; D011464:Epoprostenol; D002118:Calcium