Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta
Andrews, H.E.; Bruckdorfer, K.R.; Dunn, R.C.; Jacobs, M.
Nature 327(6119): 237-239
ISSN/ISBN: 0028-0836 PMID: 3106833 DOI: 10.1038/327237a0
The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.