LYSOPHOSPHATIDYLCHOLINE INHIBITS RECEPTOR-MEDIATED CA2-CELLS OF RABBIT AORTA( MOBILIZATION IN INTACT ENDOTHELIAL)

We have previously reported that lysophosphatidylcholine (LPC), which accumulates in oxidized LDL and atherosclerotic arteries, inhibits end othelium-dependent relaxation and modulates Ca2+ regulation in culture d bovine aortic endothelial cells. To test the effect of LPC on endoth elium-dependent relaxation and endothelial Ca2+ regulation in intact v essels, we simultaneously measured both isometric tension and endothel ial cytosolic free Ca2+ concentration ([Ca2+](i)), using fura 2, in in tact endothelial cells of aortic strips isolated from rabbits. In the aortic strips precontracted with phenylephrine, cumulative addition of acetylcholine (ACh) dose dependently induced endothelium-dependent re laxation, with an increase in endothelial [Ca2+](i), and positive corr elation was obtained between these two parameters. LPC (2 to 20 mu mol /L) inhibited both ACh (3 mu mol/L)-induced endothelium-dependent rela xation and an increase in endothelial [Ca2+](i) in a dose-dependent ma nner. On the other hand, phosphatidylcholine (20 mu mol/L) affected ne ither ACh-induced endothelium-dependent relaxation nor an increase in endothelial [Ca2+](i). LPC had no effect on endothelium-independent re laxation and a decrease in smooth muscle [Ca2+](i) induced by nitrogly cerin. Thus, the inhibitory effect of LPC on endothelium-dependent rel axation is due to the inhibition of agonist-induced Ca2+ mobilization in vascular endothelial cells, which is an essential step in the synth esis of endothelium-derived relaxing factor.