LPC in oxidized LDL elicits vasocontraction and inhibits endothelium- dependent relaxation.
Oxidized low-density lipoprotein (ox-LDL) plays an important role in the development of atherosclerosis and potentially influences the endothelial regulation of vasomotor tone. We have recently shown that lysophosphatidylcholine (LPC), a lysophospholipid contained in ox-LDL, has various pathophysiological effects. We further examined the role of LPC in the ox-LDL-induced vasoactivity in isolated pig coronary arteries. Copper-induced ox-LDL but not native LDL (n-LDL) elicited endothelium-dependent contraction during plateau contraction evoked by prostaglandin F2 alpha. Lipid extracted from ox-LDL (ox-LDL-lipid) also induced vasocontraction, but lipid of n-LDL (n-LDL-lipid) did not influence tone. When LPC was depleted from ox-LDL (i.e., defatted albumin- or phospholipase B-treated ox-LDL), vasocontraction was significantly attenuated. Synthetic palmitoyl LPC also induced endothelium-dependent vasocontraction, mimicking the response elicited by ox-LDL, but phosphatidylcholine, which exists in n-LDL and is converted to LPC during oxidative modification of LDL, did not influence the tone. Contraction to either ox-LDL or LPC was significantly attenuated by NG-monomethyl-L-arginine but not by indomethacin or superoxide dismutase. Forty minutes of incubation of coronary rings with either ox-LDL or LPC significantly attenuated endothelium-dependent vasorelaxation to thrombin without affecting vasorelaxation to endothelium-independent vasodilator nitroglycerin. In conclusion, LPC contained in lipid fraction of ox-LDL caused endothelium-dependent contraction and inhibited endothelium-dependent relaxation in isolated pig coronary arteries. The vasocontraction might be at least in part caused by LPC-mediated inhibition of endothelium-derived nitric oxide release.(ABSTRACT TRUNCATED AT 250 WORDS)
Murohara
T
T
Division of Cardiology, Kumamoto University School of Medicine, Japan.
Kugiyama
K
K
Ohgushi
M
M
Sugiyama
S
S
Ohta
Y
Y
Yasue
H
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood* / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000097:blood* / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000494:pharmacology; D013552:Swine; D013917:Thrombin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation; D019323:omega-N-Methylarginine
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D019323:omega-N-Methylarginine; D003300:Copper; D001120:Arginine; D015237:Dinoprost; D013482:Superoxide Dismutase; D013917:Thrombin; D005996:Nitroglycerin; D007213:Indomethacin