Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia-reperfusion.
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.
Cavriani
Gabriela
G
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, Cidade Universitária, São Paulo 05508-900, Brazil.
Oliveira-Filho
Ricardo Martins
RM
Trezena
Aryene Góes
AG
da Silva
Zilma Lúcia
ZL
Domingos
Helori Vanni
HV
de Arruda
Márcio José Cristiano
MJ
Jancar
Sonia
S
Tavares de Lima
Wothan
W
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002199:Capillary Permeability / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000098:blood supply / Q000503:physiopathology*; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D006146:Guanidines; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003907:Dexamethasone; D009195:Peroxidase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester