ENDOTHELIAL DYSFUNCTION EXACERBATES THE IMPAIRMENT OF RELAXATION BY LYSOPHOSPHATIDYLCHOLINE IN PORCINE CORONARY-ARTERY

1. Current evidence suggests that lysophosphatidylcholine (LPC), a com ponent found in oxidized low-density lipoprotein (Ox-LDL), inhibits en dothelium-dependent relaxation (EDR) mediated by endothelium-derived r elaxing factor (EDRF) and endothelium-derived hyperpolarizing factor ( EDHF). An objective of the present study ws to characterize the roles of the different elements of EDR in LPC-induced impairment within the procine coronary artery. Concomitantly, we sought to determine whether impairment of one component of EDR would increase the sensitivity of the endothelium to LPC. 2. Bradykinin (0.1 mmol/L-0.3 mu mol/L) relaxe d U46619 (30 nmol/L)-precontracted porcine coronary artery rings in a concentration-dependent manner. A reduction in the bradykinin-elicited response was observed in N-G-nitro-L-arginine methyl ester (L-NAME; 3 00 mu mol/L)- and ouabain (50 mu mol/L)-treated rings. Pretreatment wi th LPC (20 mu mol/L), which on its own had no effect on normal endothe lial relaxation, resulted in further inhibition of EDRF- and EDHF-indu ced relaxations. 3. Our results demonstrate that EDRF and EDHF are the primary mediators of EDR in the procine coronary artery. Our data als o show that while a low concentration of LPC (20 mu mol/L) does not im pair EDR, it can evoke vascular dysfunction following blockade of eith er the effects of EDRF or EDHF. Therefore, these data suggest that the partially damaged vascular endothelium could be more sensitive to thr eshold levels of this atherogenic phospholipid.