Lysophosphatidylcholine inhibits endothelium-dependent hyperpolarization and N omega-nitro-L-arginine/indomethacin-resistant endothelium-dependent relaxation in the porcine coronary artery.
BACKGROUND
Oxidized LDL and lysophosphatidylcholine (LPC) have been reported to inhibit the endothelium-dependent relaxation (EDR) mediated by nitric oxide. Recently, a new vasorelaxing factor, endothelium-derived hyperpolarizing factor (EDHF), which hyperpolarizes and relaxes the porcine coronary artery in the presence of N omega-nitro-L-arginine (NNA) and indomethacin (IM), has been reported. We examined whether LPC also inhibits both the EDHF-mediated relaxation and membrane hyperpolarization of the porcine coronary artery.


RESULTS
EDHF was evaluated as the bradykinin- or A23187-induced relaxation of the porcine coronary artery contracted by prostaglandin F2 alpha in the presence of NNA and IM. We also directly measured the membrane potential of the porcine coronary artery. The effects of LPC on both relaxation and membrane hyperpolarization were investigated. At concentrations of 0 to 20 mumol/L, LPC dose-dependently inhibited the NNA/IM-resistant EDR induced by bradykinin and A23187, and the relaxation was reversible after the absorption of LPC with albumin. LPC also inhibited the bradykinin- and A23187-induced hyperpolarization of the porcine coronary artery.


CONCLUSIONS
In the present study, LPC was found to inhibit not only nitric oxide-mediated but also EDHF-mediated relaxation of the porcine coronary artery. Our findings suggest a new regulatory mechanism in the atherosclerotic coronary artery.
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
H
H
Eizawa
Y
Y
Yui
R
R
Inoue
K
K
Kosuga
R
R
Hattori
T
T
Aoyama
S
S
Sasayama
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D013552:Swine
D001685:Biological Factors; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D007213:Indomethacin