Lysophosphatidylcholine inhibits receptor-mediated Ca2+ mobilization in intact endothelial cells of rabbit aorta.
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 mumol/L) inhibited both ACh (3 mumol/L)-induced endothelium-dependent relaxation and an increase in endothelial [Ca2+]i in a dose-dependent manner. On the other hand, phosphatidylcholine (20 mumol/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.
Miwa
Y
Y
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Hirata
K
K
Kawashima
S
S
Akita
H
H
Yokoyama
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology*; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000502:physiology*
D008244:Lysophosphatidylcholines; D010743:Phospholipids; D011956:Receptors, Cell Surface; D009569:Nitric Oxide; D005996:Nitroglycerin; D000109:Acetylcholine; D002118:Calcium