Paf antagonists block induction of nitric oxide synthase in cultured macrophages and vascular smooth muscle cells

Clinical and Experimental Pharmacology & Physiology
J F ArthurG J Dusting

Abstract

1. Nitric oxide (NO) synthase inhibitors and Paf antagonists abrogate hypotension in septic shock. The latter may act by blocking intracellular transduction mechanisms in vascular smooth muscle cells and inflammatory cells. We examined the effect of Paf antagonists on expression of inducible NO synthase. 2. A murine macrophage cell line (J774.2) and rat vascular smooth muscle cells (VSMC) were stimulated with lipopolysaccharide (LPS), either alone or in combination with Paf or Paf antagonists, BN 50739 or E-6123. 3. NO synthase activity in J774.2 was measured by the conversion of [3H]L-arginine to [3H]L-citrulline. Nitrite accumulation was measured in the culture medium of J774.2 and VSM. 4. BN 50739 (10 mumol/L and E-6123 (1 mumol#L) both reduced the expression of calcium-independent NO synthase activity and nitrite accumulation, while Paf alone had no effect. 5. Inhibition of NO synthase induction by Paf antagonists might afford therapeutic benefits in the management of septic shock and possibly other cardiovascular disorders.

References

Jan 1, 1992·Cardiovascular Research·C E WrightS Moncada
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A G StewartG J Dusting
Jan 21, 1983·European Journal of Pharmacology·P BessinJ Benveniste
Aug 1, 1994·The Journal of Experimental Medicine·G K HanssonE Jennische
Jan 9, 1993·Lancet·A J de BelderS Moncada

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Citations

Dec 1, 1996·Progress in Neurobiology·K M MaclennanC L Darlington
May 20, 1998·Free Radical Biology & Medicine·L G RochelleK B Adler
Jun 1, 1997·Clinical and Experimental Pharmacology & Physiology·Z L Yin, G J Dusting
Oct 1, 1996·Alcoholism, Clinical and Experimental Research·S S GreenbergT D Giles

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