Participação do oxido nitrico na resposta inflamatoria induzida pela carragenina em ratos

AUTOR(ES)
DATA DE PUBLICAÇÃO

1995

RESUMO

The effects of acute and chronic treatment with the nitric oxide (NO) synthase inhibitor N(J)-nitro-L-arginine methyl ester (L-NAME) and its inactive enantiomer N(J)-nitro-D-arginine methyl ester (D-NAME) on the inflammatory responses (rat paw oedema, vascular permeability and pleurisy) induced by carrageenin in rats have been investigated. Changes in the rat paw volume were measured with a hydroplethysmometer at 1, 2, 3 and 4 hours afier the injection of carrageenin. When recersary, L-NAME or D-NAME was administered subplantarly, intrapleurally or intravenously immediately before the injection of carrageenin. The subplantar (0.15 :1.0 Ilmollpaw) or intravenous (10-100 Ilmol/kg) injection of L-NAME dose-dependently inhibited the carrageenin-induced paw oedema. The administration of D-NAME by either route (1 ~lmol/paw or 100 Ilmol/kg) had no effect on the foregoing oedema. The inhibition of paw oedema by L-NAME was significantly reversed by the local administration of the prostacyclin analogue iloprost (0.3 Ilmol/paw). The carrageenin-induced leucocyte migration into the pleural cavity was also dose-dependently inhibited by the intravenous (10-100 Ilmol/kg) or intrapleural (3-10 Ilmol/cavity) injection of L-NAME. D-NAME (1 Ilmol/paw or 350 Ilmol/kg) had no effect on leucocyte migration. Our results indicate that the inhibition of both paw oedema and cell migration caused by acute L-NAME treatment is subsequent to a reduction in local microvascular blood flow. Chronic inhibition of NO biosynthesis was achieved by including L-NAME in the drinking water to give an in take of approximately 75 Ilmol/ratlday for two and four weeks. Control animais received either tap water alone or the inactive enantiomer D-NAME. Since chronic NO inhibition increases blood pressure, we compared the resulting paw oedema with that produced in rats made hypertensive by occlusion of the left renal artery (2K-1 C). In a separate set of experiments, L-NAME-treated animais concomitantly received captopril (140 IlmollraUday) to prevent hypertension. Animais chronicaHy treated with L-NAME (but not D-NAME) for two or four weeks developed hypertension to the same extent as 2K-1C rats. Carrageenin-induced paw oedema was significantly reduced in rats chronicaHy treated with L-NAME, but not in those receiving 0NAME or in 2K-1C animais. The subplantar injection of iloprost significantly reversed the inhibition of paw oedema caused by L-NAME. Captopril (140 Ilmollrat day) lowered the high blood pressure levels induced by L-NAME (p<0.05) but did not significantly affect the inhibition of paw oedema by L-NAME. No changes in vascular permeability, as assessed by Evans blue extravasation, were observed in L-NAME-treated animais. The chronic treatment with L-NAME for two or four weeks did n ot inhibit carrageenin-induced leucocyte migration into the pleural cavity. It is concluded that although carrageenin-induced paw oedema is reduced in L-NAME-treated rats, this response reflects a decrease in local blood flow rather than an effect on vascular permeability. Furthermore, the chronic inhibition of biosynthesis does not affect vascular permeability and ceH migration in the pleurisy model

ASSUNTO(S)

inflamação oxido nitrico - inflamação carragenina

ACESSO AO ARTIGO

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