IMMEDIATE RELEASE OF A NITRIC OXIDE-LIKE FACTOR FROM BOVINE AORTIC ENDOTHELIAL-CELLS BY ESCHERICHIA-COLI LIPOPOLYSACCHARIDE

Incubation of human washed platelets with bovine aortic endothelial cells (ECs) treated with indomethacin resulted in an inhibition of thrombin-induced platelet aggregation that was dependent on the number of ECs added. Preincubation of ECs with Escherichia coli lipopolysaccharide (LPS; 0.5-2.0 μg/ml) for 1 min significantly enhanced their inhibitory activity. This effect was potentiated by superoxide dismutase (60 units/ml) and reversed by oxyhemoglobin (5-10 μM), indicating that the inhibition was due to the release of endothelium-derived relaxing factor (nitric oxide). When the ECs were pretreated with N(G)-monomethyl-L-arginine (30-300 μM) before LPS, the antiaggregatory activity was strongly reduced. The reduction of activity by N(G)-monomethyl-L-arginine was reversed by L-arginine (100 μM) but not by D-arginine (10 μM). Under similar conditions, LPS also enhanced the antiaggregatory activity of ECs grown on beads. The immediate enhancement by LPS of the release of endothelium-derived relaxing factor from endothelial cells may contribute to the rapid fall in blood pressure associated with endotoxin shock in vivo.