PAF ANTAGONISTS BLOCK INDUCTION OF NITRIC-OXIDE SYNTHASE IN CULTURED MACROPHAGES AND VASCULAR SMOOTH-MUSCLE CELLS

被引:15
作者
ARTHUR, JF [1 ]
SHAHIN, S [1 ]
DUSTING, GJ [1 ]
机构
[1] UNIV MELBOURNE,DEPT PHYSIOL,PARKVILLE,VIC 3052,AUSTRALIA
关键词
LIPOPOLYSACCHARIDE; MACROPHAGES; NITRIC OXIDE SYNTHASE; PLATELET-ACTIVATING FACTOR; PAF ANTAGONISTS; VASCULAR SMOOTH MUSCLE;
D O I
10.1111/j.1440-1681.1995.tb02041.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 [H-3]L-arginine to [H-3]L-citrulline. Nitrite accumulation was measured in the culture medium of J774.2 and VSM. 4. BN 50739 (10 mu mol/L) and E-6123 (1 mu mol/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.
引用
收藏
页码:452 / 454
页数:3
相关论文
共 9 条
  • [1] Bessin P., Bonnet J., Soulard C., Desgroux L., Pelas I., Benveniste J., Acute circulatory collapse caused by platelet‐activating factor (PAF‐acether) in dogs, European Journal of Pharmacology, 86, pp. 403-413, (1989)
  • [2] Camussi G., Bussolino F., Salvidio G., Baglioni C., Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorpho‐nuclear neutrophils, and vascular endothelial cells to synthesize and release platelet‐activating factor, Journal of Experimental Medicine, 166, pp. 1390-1396, (1987)
  • [3] De Belder A.J., Radomski M.W., Why H.J.F., Et al., Nitric oxide synthase activities in human myocardium, Lancet, 341, pp. 84-85, (1993)
  • [4] Doebber T.W., Wu M.S., Robbins J.C., Choy G.M., Chang M.N., Shen T.Y., Platelet activating factor (PAF) involvement in endotoxin‐induced hypotension in rats. Studies with PAF‐receptor antagonist kadsurenone, Biochemical and Biophysical Research Communications, 127, pp. 799-808, (1985)
  • [5] Hansson G.K., Yong-jinn G., Holm J., Hardhammar P., Wennmalm A., Jennische E., Arterial smooth muscle cells express nitric oxide synthase in response to endothelial injury, Journal of Experimental Medicine, 180, pp. 733-738, (1994)
  • [6] Lynch J.M., Lotner G.Z., Betz S.J., Henson P.M., The release of a platelet‐activating factor by stimulated rabbit neutrophils, Journal of Immunology, 123, pp. 1219-1226, (1979)
  • [7] Stewart A.G., Dubbin P.N., Harris T., Dusting G.J., Platelet‐activating factor may act as a second messenger in the release of eicosanoids and superoxide anions from leucocytes and endothelial cells, Proceedings of the National Academy of Science USA, 87, pp. 3215-3219, (1990)
  • [8] Szabo C., Wu C-C., Mitchell J.A., Gross S.S., Thiemermann C., Vane J., Platelet‐activating factor contributes to the induction of nitric oxide synthase by bacterial lipopolysaccharide, Circulation Research, 73, pp. 991-999, (1993)
  • [9] Wright C., Rees D., Moncada S., Protective and pathological roles of nitric oxide in endotoxic shock, Cardiovascular Research, 26, pp. 48-57, (1992)