Diazepam effects on carrageenan-induced inflammatory paw edema in rats: role of nitric oxide

Autor(es)

Lazzarini‚ R. ; Maiorka‚ P.C. ; Liu‚ J. ; Papadopoulos‚ V. ; Palermo-Neto‚ J.

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 78, n. 26, p. 3027-3034, 2006.

Resumo

High doses of diazepam (10.0-20.0 mg/kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenan administration. This effect was attributed to an action of diazepam on the peripheral-type benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory cells. The present study was undertaken to analyze the involvement of nitric oxide (NO) on the effects of diazepam on carragenan-induced paw edema in rats (CIPE) and to look for the presence of PBR and inducible/constitutive NO synthases (NOS) on slices taken from the inflamed paws of diazepam-treated rats. For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg N omega-nitro-L-arginine (L-NAME), L-arginine (300.0 mg/kg), the true precursor of NO, and D-arginine (300.0 mg/kg), its false substrate, were also used. The following results were obtained: (1) diazepam (10.0 and 20.0 mg/kg) decreased CIPE values in a dose- and tlime-dependent way; (2) diazepam effects on CIPE were increased by L-NAME pretreatment; (3) treatment with L-arginine but not with D-arginine reverted at least in pail the decrements of CIPE values observed after diazepam administration; (4) PBR were found in endothelial and inflammatory cells that migrated to the inflammatory site at the rat paw; (5) confocal microscopy showed the presence of both PBR and NOS in endothelial and inflammatory cells taken from inflamed paw tissues of rats treated with diazepam a finding not observed in tissues provided from rats treated with diazepam's control solution. These results suggest an important role for NO on the effects of diazepam on CIPE. Most probably, these effects reflect a direct action of diazepam on PBR present in the endothelium of the microvascular ambient and/or on immune/inflammatory cells. An action like that would lead, among other factors, to a decrease in NO, generated by NO synthase, and thus in the mechanisms responsible for CIPE. (c) 2005 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 99/04228-7 - Neuroimunomodulação: efeito do estresse e de fármacos com ação no sistema nervoso central sobre a resposta imune/inflamatória
• Beneficiário: João Palermo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 99/04128-2 - O Diazepam e a resposta inflamatória induzida pela carragenina em ratos: parte II: mecanismo de ação
• Beneficiário: Ricardo Lazzarini
• Modalidade de apoio: Bolsas no Brasil - Doutorado