Oxidized Low Densit Lipoproteins Inhibit Relaxations of Porcine Coronary Arteries Role of Scavenger Receptor and Endothelium-Derived Nitric Oxide

Background. We studied the effects of low density lipoprotein (LDL) on endothelium function. Methods and Results. Porcine epicardial and intramyocardial coronary arteries suspended in organ chambers for isometric tension recording were exposed to LDL for 2 hours and were then washed. In epicardial coronary arteries, oxidized LDL (30-300,ug/mI) but not native LDL or lysolecithin inhibited endothelium-dependent relaxations to serotonin, thrombin, and aggre-gating platelets (5,000-75,000/,ul). Endothelium-dependent relaxations to bradykinin and A23187 and endothelium-independent relaxations to SIN-1 were unaffected by oxidized LDL. In intramyocardial coronary arteries, oxidized LDL had no appreciable effect on relaxations to serotonin. The effect of oxidized LDL on the response to serotonin in epicardial coronary arteries was completely prevented by dextran sulfate (10 jiglml). The inhibitory effect of oxidized LDL persisted in the presence of pertussis toxin. Similar to the lipoproteins, L-NG-monomethyl arginine (L-NMMA) reduced relaxations to serotonin but not to bradykinin in epicardial coronary arteries. In the presence of L-NMMA, oxidized LDL further reduced the response to serotonin. In arteries in which relaxations to serotonin were inhibited by oxidized LDL, L-arginine but not D-arginine induced a full relaxation. Pretreatment with L-arginin