Oxidized low density lipoprotein inhibits bradykinin-induced phosphoinositide hydrolysis in cultured bovine aortic endothelial cells.
Vascular endothelial cells, in response to various neurohumoral and physical stimuli, produce an endothelium-derived relaxing factor, a substance which regulates vascular tone. We have demonstrated that oxidized low density lipoprotein (LDL) inhibits endothelium-dependent relaxation. We studied the effect of oxidized LDL on inositol phosphates formation stimulated with bradykinin (BK) in cultured bovine aortic endothelial cells. BK elicited a rapid generation of inositol phosphates from inositol phospholipids. Accumulation of inositol 1,4,5-trisphosphate (IP3) stimulated with BK (0.1 microM) was markedly inhibited by oxidized LDL. However, native LDL had little effect on BK-induced accumulation of IP3. From these results, oxidized LDL inhibits receptor-mediated phosphoinositides hydrolysis and modulates the endothelial function.
Hirata
K
K
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
Akita
H
H
Yokoyama
M
M
D000818:Animals; D001011:Aorta; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010716:Phosphatidylinositols / Q000378:metabolism*
D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D001920:Bradykinin