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 re ported to inhibit the endothelium-dependent relaxation (EDR) mediated by nitric oxide. Recently, a new vasorelaxing factor, endothelium-deri ved hyperpolarizing factor (EDHF), which hyperpolarizes and relaxes th e porcine coronary artery in the presence of N-omega-nitro-L-arginine (NNA) and indomethacin (IM), has been reported. We examined whether LP C also inhibits both the EDHF-mediated relaxation and membrane hyperpo larization of the porcine coronary artery. Methods and Results EDHF wa s evaluated as the bradykinin- or A23187-induced relaxation of the por cine coronary artery contracted by prostaglandin F-2 alpha in the pres ence of NNA and IM. We also directly measured the membrane potential o f the porcine coronary artery. The effects of LPC on both relaxation a nd membrane hyperpolarization were investigated. At concentrations of 0 to 20 mu mol/L, LPC dose-dependently inhibited the NNA/IM-resistant EDR induced by bradykinin and A23187, and the relaxation was reversibl e after the absorption of LPC with albumin. LPC also inhibited the bra dykinin- 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 p orcine coronary artery. Our findings suggest a new regulatory mechanis m in the atherosclerotic coronary artery.