The role of endothelial cell Ca2+ store release in the regulation of microvascular permeability in vivo.
Microvascular permeability is regulated by changes in intracellular calcium concentration. The mechanism by which this increase in calcium determines permeability under normal conditions and during stimulation with agonists remains to be elucidated. In order to determine whether calcium release from intracellular stores could contribute towards the regulation of vascular permeability, hydraulic conductivity (Lp) was measured in frog mesenteric microvessels during stimulation of the endothelial cells of these vessels with agonists that release calcium from the intracellular stores. ATP (which acts through activation of inositol 1,4,5-trisphosphate (IP3) receptors) increased Lp in the absence of calcium influx across the plasma membrane 2.3 +/- 0.3 fold (mean +/- s.e.m., P < 0.01, n = 8), which was less than the increase in the presence of calcium influx (3.1 +/- 1.1 fold). Caffeine (which acts through activation of ryanodine receptors) also increased Lp in the absence of calcium influx across the plasma membrane 3.8 +/- 1.0 fold (P < 0.01, n = 9), but by at least as much as it does in the presence of calcium influx (2.8 +/- 0.5 fold). It is surprising that there was a strong positive correlation between the size of the response during store release and the baseline permeability (r = 0.91 for ATP, r = 0.75 for caffeine). This suggests that the filling state of the stores may regulate the baseline permeability of the microvessels.
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Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, Southwell Street, University of Bristol, Bristol BS2 8EJ, UK. dave.bates@bristol.ac.uk
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002199:Capillary Permeability / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D011896:Rana temporaria; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013152:Splanchnic Circulation
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium