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 micrograms/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 microM), indicating that the inhibition was due to the release of endothelium-derived relaxing factor (nitric oxide). When the ECs were pretreated with NG-monomethyl-L-arginine (30-300 microM) before LPS, the antiaggregatory activity was strongly reduced. The reduction of activity by NG-monomethyl-L-arginine was reversed by L-arginine (100 microM) but not by D-arginine (100 microM). 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.
Salvemini
D
D
William Harvey Research Institute, Saint Bartholomew's Hospital Medical College, London, United Kingdom.
Korbut
R
R
Anggård
E
E
Vane
J
J
D000818:Animals; D001011:Aorta; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004926:Escherichia coli; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D013482:Superoxide Dismutase / Q000494:pharmacology
D008070:Lipopolysaccharides; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D001920:Bradykinin; D007213:Indomethacin