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Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1561-1567

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1561-1567.)
© 1997 American Heart Association, Inc.


Articles

Lysophosphatidylcholine Inhibits Receptor-Mediated Ca2+ Mobilization in Intact Endothelial Cells of Rabbit Aorta

Yoichi Miwa; Ken-ichi Hirata; Seinosuke Kawashima; Hozuka Akita; ; Mitsuhiro Yokoyama

From the First Department of Internal Medicine, Kobe University School of Medicine, Japan.

Correspondence to Mitsuhiro Yokoyama, MD, First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.

Abstract We have previously reported that lysophosphatidylcholine (LPC), which accumulates in oxidized LDL and atherosclerotic arteries, inhibits endothelium-dependent relaxation and modulates Ca2+ regulation in cultured bovine aortic endothelial cells. To test the effect of LPC on endothelium-dependent relaxation and endothelial Ca2+ regulation in intact vessels, we simultaneously measured both isometric tension and endothelial cytosolic free Ca2+ concentration ([Ca2+]i), using fura 2, in intact 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 relaxation, with an increase in endothelial [Ca2+]i, and positive correlation was obtained between these two parameters. LPC (2 to 20 µmol/L) inhibited both ACh (3 µmol/L)-induced endothelium-dependent relaxation and an increase in endothelial [Ca2+]i in a dose-dependent manner. On the other hand, phosphatidylcholine (20 µmol/L) affected neither ACh-induced endothelium-dependent relaxation nor an increase in endothelial [Ca2+]i. LPC had no effect on endothelium-independent relaxation and a decrease in smooth muscle [Ca2+]i induced by nitroglycerin. Thus, the inhibitory effect of LPC on endothelium-dependent relaxation is due to the inhibition of agonist-induced Ca2+ mobilization in vascular endothelial cells, which is an essential step in the synthesis of endothelium-derived relaxing factor.


Key Words: phospholipids • vascular endothelium • lysophosphatidylcholine • endothelium-derived relaxing factor • intracellular calcium




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