High-affinity arginine transport of bovine aortic endothelial cells is impaired by lysophosphatidylcholine.
The mechanisms of endothelial dysfunction characterized by the impaired nitric oxide (NO) release have not yet been clarified. Because the phenomenon is mimicked in vitro by the application of oxidized LDL and its major lipid constituent, lysophosphatidylcholine (LPC), we analyzed their effects on the arginine-NO system, especially on the arginine transport system. LPC inhibited NO release induced by ADP in cultured bovine aortic endothelial cells. The inhibition was attenuated by the excess amount of extracellular arginine. LPC was found to inhibit the arginine transport in bovine aortic endothelial cells, which is mediated by high- and low-affinity components. LPC predominantly impaired the high-affinity component. In the presence of a high concentration of arginine, LPC showed apparently no inhibition of arginine transport, because the low-affinity transporter compensated for the activity. Taken together, the impairment of the high-affinity transport system might account for the inhibition of NO release by LPC. LPC also inhibited arginine transport in the intima of intact bovine aorta. Furthermore, LPC inhibited the activity of the high-affinity arginine transporter in endothelial cells, in the cationic amino acid transporter-1 expressed in COS-7 cells. The activity of cationic amino acid transporter-1 might be important for the prevention of endothelial dysfunction.
Kikuta
K
K
Department of Pharmacology, and Neurosurgery, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Sawamura
T
T
Miwa
S
S
Hashimoto
N
N
Masaki
T
T
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001120:Arginine / Q000493:pharmacokinetics*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D014343:Trypan Blue
D003470:Culture Media; D008244:Lysophosphatidylcholines; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue; D002118:Calcium