Effect of low density lipoprotein on adenosine receptor-mediated coronary vasorelaxation

The effect of low density lipoprotein (LDL) on vasorelaxation of porcine coronary artery rings induced by the adenosine analogs, NECA and CGS21680 was investigated. Preincubation of rings with native LDL (n-LDL, 100 ug/ml and 200 ug/ml) for 4 hr in the absence and presence of copper sulfate (5 uM) selectively attenuated the endothelium-dependent relaxations produced by NECA and CGS-21680. LDL also inhibited the production of NO evoked by NECA and CGS-21680 in endothelium-intact tissues. These effects of LDL were associated with oxidation of the lipoprotein. The inhibitory effects of LDL on both tissue relaxations and NO production as well as its oxidative modification were all reversed by high density lipoprotein (HDL, 100 ug/ml) In contrast, a relatively short period (20 min) of incubation with n-LDL produced no alterations of the relaxations and NO production elicited by NECA and CGS-21680. Under these conditions, no significant oxidation of LDL was detected. These results indicate that prolonged incubation of coronary artery rings with n-LDL causes attenuation of endotheliumdependent vasorelaxation and NO generation induced by adenosine receptor stimulation and these effects are associated with oxidation of the lipoprotein. It is hypothesized that in atherosclerosis, endothelium-dependent coronary artery responses mediated by adenosine receptors are impaired. (Supported by HL-27339 and Minority Supplement to HL-50049).