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

• Published in: European journal of pharmacology 2004-06, Vol.494 (2), p.241-249
• Main Authors: Cavriani, Gabriela, Oliveira-Filho, Ricardo Martins, Trezena, Aryene Góes, da Silva, Zilma Lúcia, Domingos, Helori Vanni, de Arruda, Márcio José Cristiano, Jancar, Sonia, Tavares de Lima, Wothan
• Format: Article
• Language: English
• Subjects: Adult respiratory distress syndrome; Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Capillary Permeability - physiology; Dexamethasone - pharmacology; Gastroenterology. Liver. Pancreas. Abdomen; Guanidines - pharmacology; Inflammation - pathology; Inflammation - physiopathology; Intestinal ischemia/reperfusion; Intestines - blood supply; Intestines - physiopathology; Lung - enzymology; Lung - pathology; Lung inflammation; Male; Medical sciences; Neutrophil accumulation; Neutrophil Infiltration - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - physiology; NO(Nitric oxide); Other diseases. Semiology; Peroxidase - metabolism; Pulmonary Circulation - physiology; Rats; Rats, Wistar; Regional Blood Flow; Reperfusion Injury - physiopathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Necrosis Factor-alpha - metabolism; Vascular permeability
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.04.048

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.