Vol. 282, Issue 2, 851-857, 1997

Effect of Low Density Lipoprotein on Adenosine Receptor-Mediated Coronary Vasorelaxation in Vitro¹

Worku Abebe and S. Jamal Mustafa

Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina

We investigated the effect of low density lipoprotein (LDL) on vasorelaxations and nitric oxide generation induced by the adenosine analogs, 5-(N-ethylcarboxamide)adenosine, 2-p-(2-carboxyethyl)phenylethyl-amino-5N-ethylcarboxamidoadenosine and/or 2-chloroadenosine in porcine coronary artery rings in vitro. Preincubation of tissues with native LDL (100 and 200 µg/ml) for 4 hr in the absence or presence of copper sulfate (5 µM) selectively attenuated the endothelium-dependent relaxations elicited by 5-(N-ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl)phenylethyl-amino-5N-ethylcarboxamideoadenosine without altering the response to 2-chloroadenosine which produced endothelium-independent relaxation. The 4-hr exposure of tissues to native LDL (100 µg/ml) also inhibited the production of nitrite induced by 5-(N-ethylcarboxamide)adenosine in endothelium-intact rings. These effects were associated with enhanced oxidation of the lipoprotein. The inhibitory action of LDL on tissue relaxations and nitrite generation as well as the oxidation of the lipoprotein were all prevented by high density lipoprotein (100 µg/ml). In contrast, a relatively short period (20 min) of tissue incubation with native LDL produced no alterations of the relaxations and nitrite production evoked by 5-(N-ethylcarboxamide)adenosine and 2-p-(2-carboxyethyl)phenylethyl-amino-5N-ethylcarboxamidoadenosine. Under this condition, the oxidation of LDL was not also significantly altered. In conclusion, the results indicate that in coronary artery LDL, with oxidative modification, causes attenuation of nitric oxide-mediated endothelial responses induced by adenosine receptors activation, and this effect is prevented by high density lipoprotein. Such modulation may be of importance in hypercholesterolemia and in the development of atherosclerosis.