Nitric oxide decreases endothelial activation by rat experimental severe pancreatitis-associated ascitic fluids

Atsushi Masamune, Tooru Shimosegawa, Akihiko Satoh, Motokazu Fujita, Yoshitaka Sakai, Takayoshi Toyota

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

To clarify the roles of nitric oxide (NO) in acute pancreatitis (AP), we examined the effects of NO on the endothelial activation induced by ascitic fluids from rats with experimental severe AP. Necrotizing hemorrhagic pancreatitis was induced in male Wistar rats with sodium taurocholate. Six hours later, peritoneal exudates were collected, centrifuged, and human umbilical vein endothelial cells were treated with the supernatants. Then (a) the mRNA level of endothelial-type NO synthase (ecNOS) was examined by reverse transcription-polymerase chain reaction; (b) effects of an NO donor, sodium nitroprusside (SNP) and an inhibitor of NOS, N(ω)-nitro-L-arginine (L-NNA) on the ascitic fluids-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-8 were assessed by enzyme-linked immunoassay; (c) nuclear translocation of nuclear factor-kappa B (NF-κB) was examined by electrophoretic mobility shift assay; and (d) effects of SNP and L-NNA on the adhesion of U937 cells to endothelial monolayer were assessed. The ecNOS mRNA level was decreased by the ascitic fluids; ascitic fluids - induced expression of adhesion molecules and interleukin-8 as well as the nuclear translocation of NF-κB were attenuated by SNP, whereas L-NNA augmented them; and the effects on the endothelial activation were paralleled by the altered adhesion of U937 cells to endothelium. The ability of NO to limit endothelial activation and inhibit leukocyte adhesion might contribute to its antiinflammatory properties in AP.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalPancreas
Volume20
Issue number3
DOIs
Publication statusPublished - 2000 Apr 1

Keywords

  • Acute pancreatitis
  • Ascitic fluids
  • Endothelium
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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