SELECTIVE ENHANCEMENT OF 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF PORCINE CORONARY-ARTERY BY OXIDIZED LOW-DENSITY-LIPOPROTEIN

Oxidatively modified low-density lipoprotein (LDL) may be involved in the vasomotor disturbances associated with hyper cholesterolemia and a therosclerosis, but effects of this lipoprotein on agonist-induced cor onary vasoconstriction have not been reported. This study determined t he effects of oxidized LDL on contraction of isolated porcine coronary arteries to several contractile agonists and investigated the mechani sm of these effects. Oxidized LDL (10-100 mu g/ml) enhanced 5-hydroxyt ryptamine (5-HT)-induced contraction in a concentration-dependent mann er, whereas native LDL (100 mu g/ml) had no effect. Enhancement of 5-H T-induced contraction was dependent on the presence of endothelium and blocked by L-N-G-monomethyl-arginine (100 mu M). Oxidized LDL (100 mu g/ml) similarly inhibited endothelium- and nitric oxide-dependent rel axation induced by 5-HT, but had no effect on relaxation induced by so dium nitroprusside. Furthermore, contraction to U46619 and acetylcholi ne, agonists that did not mediate endothelium-dependent relaxation, wa s unaffected by oxidized LDL (100 mu g/ml). Lysophosphatidylcholine (1 0-30 mu mol/liter) also enhanced 5-HT-induced contraction and inhibite d 5-HT-induced, endothelium-dependent relaxation. Endothelium-dependen t relaxation to bradykinin was unaffected by lysophosphatidylcholine ( 20 mu M). Thus, oxidized LDL enhanced 5-HT-induced coronary vasoconstr iction in an endothelium dependent manner, actions that were mimicked by relevant concentrations of lysophosphatidylcholine. These in vitro effects of oxidized LDL mimicked effects of hypercholesterolemia and a therosclerosis on 5-HT vasoactivity in human coronary arteries in vivo , suggesting that oxidized LDL may play an important role in the devel opment of vasomotor disturbances in these pathologies.