Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells.
Vascular endothelium, which produces endothelium-derived relaxing and constricting factors, plays an important role in regulating the vascular tone. We recently demonstrated that oxidized low density lipoprotein inhibited endothelium-dependent relaxation and that lysophosphatidylcholine accumulated during the oxidative modification of low density lipoprotein was the essential substance for the inhibition of endothelium-dependent relaxation. To clarify the mechanisms of the inhibitory effect of lysophosphatidylcholine, we used a bioassay system to investigate the effect of lysophosphatidylcholine on the production and/or release of endothelium-derived relaxing factor and its effect on the cytosolic Ca2+ level ([Ca2+]i) and phosphoinositide hydrolysis in cultured bovine aortic endothelial cells. [Ca2+]i was monitored by the fura 2 method, and the accumulation of inositol phosphates in cells labeled with myo-[2-3H]inositol was measured. Bioassay experiments showed that lysophosphatidylcholine inhibited the production and/or release of endothelium-derived relaxing factor from cultured endothelial cells. Lysophosphatidylcholine (5-20 micrograms/ml) induced a biphasic increase in [Ca2+]i, which consisted of a rapid increase followed by a sustained increase, and the initial component was a result of mobilization from intracellular Ca2+ stores without detectable synthesis of inositol 1,4,5-trisphosphates. Furthermore, lysophosphatidylcholine (5-20 micrograms/ml) dose-dependently inhibited both phosphoinositide hydrolysis and the increases in [Ca2+]i evoked by bradykinin. These results indicate that the impairment of endothelium-dependent relaxation induced by lysophosphatidylcholine is due to the inhibition of phosphoinositide hydrolysis and the subsequent increases in [Ca2+]i in endothelial cells. Lysophosphatidylcholine that accumulates in oxidized low density lipoprotein and atherosclerotic arteries may play an important role in the modification of endothelial function.
Inoue
N
N
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Hirata
K
K
Yamada
M
M
Hamamori
Y
Y
Matsuda
Y
Y
Akita
H
H
Yokoyama
M
M
D000818:Animals; D001011:Aorta; D001681:Biological Assay; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006868:Hydrolysis; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000032:analysis / Q000037:antagonists & inhibitors*; D010716:Phosphatidylinositols / Q000378:metabolism*
D008244:Lysophosphatidylcholines; D010716:Phosphatidylinositols; D009569:Nitric Oxide; D001920:Bradykinin; D002118:Calcium