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Type: Artigo
Title: Different mechanisms underlie the effects of acute and long-term inhibition of nitric oxide synthases in antigen-induced pulmonary eosinophil recruitment in BALB/C mice
Author: Lintomen, Leticia
Mendes, Gustavo D.
De Nucci, Gilberto
Antunes, Edson
Souza-Filho, Luis Gustavo
Camargo, Enilton A.
Jancar, Sonia
Ferreira, Tatiane
Landgraf, Richardt G.
Teixeira, Simone A.
Muscara, Marcelo N.
Abstract: Nitric oxide synthase (NOS) inhibitors are largely used to evaluate the NO contribution to pulmonary allergy, but contrasting data have been reported. In this study, pharmacological, biochemical and pharmacokinetic assays were performed to compare the effects of acute and long-term treatment of BALB/C mice with the non-selective NOS inhibitor L-NAME in ovalbumin (OVA)-challenged mice. Acute L-NAME treatment (50 mg/kg, gavage) significantly reduced the eosinophil number in bronchoalveolar lavage fluid (BALF). The inducible NOS (iNOS) inhibitor aminoguanidine (20 mg/kg/day in the drinking water) also significantly reduced the eosinophil number in BALF In contrast, 3-week L-NAME treatment (50 and 150 mg/kg/day in the drinking water) significantly increased the pulmonary eosinophil influx. The constitutive NOS (cNOS) activity in brain and lungs was reduced by both acute and 3-week L-NAME treatments. The pulmonary iNOS activity was reduced by acute L-NAME (or aminoguanidine), but unaffected by 3-week L-NAME treatment. Acute L-NAME (or aminoguanidine) treatment was more efficient to reduce the NO(x) levels compared with 3-week L-NAME treatment. The pharmacokinetic study revealed that L-NAME is not bioavailable when given orally. After acute L-NAME intake, serum concentrations of the metabolite N(omega)-nitro-L-arginine decreased from 30 min to 24 h. In the 3-week L-NAME treatment, the N(omega)-nitro-L-arginine concentration was close to the detection limit. In conclusion, 3-week treatment with L-NAME yields low serum N(omega)-nitro-L-arginine concentrations, causing preferential inhibition of cNOS activity. Therefore, eosinophil influx potentiation by 3-week L-NAME treatment may reflect removal of protective cNOS-derived NO, with no interference on the ongoing inflammation due to iNOS-derived NO
Subject: Disponibilidade biológica
Óxido nítrico sintase
NG-nitroarginina metil éster
Country: Reino Unido
Editor: Elsevier
Citation: PULMONARY PHARMACOLOGY & THERAPEUTICS, v.22, n.1, p.1-8, 2009
Rights: fechado
Identifier DOI: 10.1016/j.pupt.2008.10.003
Date Issue: 2009
Appears in Collections:IQ - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos

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