Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia-reperfusion

Eur J Pharmacol. 2004 Jun 28;494(2-3):241-9. doi: 10.1016/j.ejphar.2004.04.048.

Abstract

We investigated the effect of two inhibitors of nitric oxide (NO) synthesis, N(w)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, on lung inflammation caused by intestinal ischemia/reperfusion in rats. Relative to the sham-operated rats, intestinal ischemia/reperfusion (ischemia: 45 min; reperfusion: 30 min, 2 and 4 h) induced neutrophil recruitment (increased myeloperoxidase activity) and increased microvascular permeability (Evans blue dye extravasation) in the lungs and increased tumor necrosis factor (TNF) levels in the serum (L-929 cytotoxicity assay). L-NAME given before the ischemia exacerbated neutrophil accumulation, plasma extravasation, serum TNF and caused death of the animals, which was prevented by concomitant injection of L-arginine. Lung and systemic effects of intestinal ischemia/reperfusion were not modified when L-NAME was given just before reperfusion. Treatment with aminoguanidine inhibited plasma extravasation without affecting the other parameters evaluated. Dexamethasone reduced all the parameters. Our results indicate that during intestinal ischemia/reperfusion both constitutive and inducible NO synthases are called to exert a differential modulatory effect on lung inflammation and that maintenance of adequate levels of NO during ischemia is essential for the animals survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Capillary Permeability / physiology*
  • Dexamethasone / pharmacology
  • Guanidines / pharmacology
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Intestines / blood supply
  • Intestines / physiopathology*
  • Lung / enzymology
  • Lung / pathology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neutrophil Infiltration / physiology*
  • Nitric Oxide / physiology*
  • Peroxidase / metabolism
  • Pulmonary Circulation / physiology*
  • Rats
  • Rats, Wistar
  • Regional Blood Flow
  • Reperfusion Injury / physiopathology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Guanidines
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Dexamethasone
  • Peroxidase
  • pimagedine
  • NG-Nitroarginine Methyl Ester