Role of endothelial Ca2+ stores in the regulation of hydraulic conductivity of Rana microvessels in vivo

Vascular permeability is regulated by endothelial cytosolic Ca2+ concentration ([Ca2+](i)). To determine whether vascular permeability is dependent o extracellular Ca2+ influx or release of Ca2+ from stores, hydraulic conductivity (L-p) was measured in single perfused frog mesenteric microvessels in the presence and absence of Ca2+ influx and store depletion. Prevention of Ca2+ reuptake into stores by sarco(endo)plasmic reticulum. Ca2+-ATPase (SERCA) inhibition increased L-p in the absence of extracellular Ca2+ influx. L-p was further increased when Ca2+ influx was restored. Depletion of the Ca2+ stores with ionomycin and SERCA inhibition increased L-p in the presence and the absence of extracellular Ca2+ influx. However, store depletion in itself did not significantly increase L-p in the absence of active Ca2+ release from stores into the cytoplasm. There was a significant positive correlation between baseline permeability and the magnitude of the responses to both Ca2+ store release and Ca2+ influx, indicating that the Ca2+ regulating properties of the endothelial cells may regulate the baseline L-p. To investigate the role of Ca2+ stores in regulation of L-p, the relationship between SERCA inhibition and store release was studied. The magnitude of the L-p increase during SERCA inhibition significantly and inversely correlated with that during store release by Ca2+ ionophore, implying that the degree of store depletion regulates the size of the increase on L-p. These data show that microvascular permeability in vivo can be increased by agents that release Ca2+ from stores in the absence of Ca2+ influx. They also show that capacitative Ca2+ entry results in increased L-p and that the size of the permeability increase can be regulated by the degree of Ca2+ release.