EFFECT OF CHRONIC NITRIC-OXIDE SYNTHESIS INHIBITION ON THE INFLAMMATORY RESPONSES INDUCED BY CARRAGEENAN IN RATS

The effect of chronic inhibition of nitric oxide (NO) biosynthesis has been investigated in two models of acute inflammation induced by carr ageenin, i.e., paw oedema and pleurisy. Chronic inhibition of NO biosy nthesis was achieved by including N-omega-nitro-L-arginine methyl este r (L-NAME) in the drinking water to give a dose of approximately 75 mu mol/rat/day for 2 and 4 weeks. Control animals received either tap wa ter alone or the inactive enantiomer D-NAME. Since chronic NO inhibiti on increases blood pressure, rats made hypertensive (2 kidney-1 clip m odel; 2K-1C) were used to evaluate the effect of hypertension on the c arrageenin-induced paw oedema. In a separate set of experiments, L-NAM E-treated animals concomitantly received captopril (140 mu mol/rat/day ) to prevent hypertension. Animals chronically treated with L-NAME (bu t not D-NAME) for 2 and 4 weeks developed hypertension to the same ext ent as 2K-1C rats. Carrageenin-induced paw oedema was significantly re duced in animals chronically treated with L-NAME, but not with D-NAME or in 2K-1C rats. Subplantar injection of iloprost completely reversed the inhibition of paw oedema caused by L-NAME. Captopril (140 mu mol/ rat/day) significantly lowered the high blood pressure levels induced by L-NAME but did not significantly affect the inhibition of paw oedem a caused by L-NAME. No changes in vascular permeability, as assessed b y Evans blue extravasation, were observed in L-NAME-treated animals. T he chronic treatment with L-NAME for 2 and 4 weeks did not inhibit car rageenin-induced leucocyte migration and fluid exudation into the pleu ral cavity. Although carrageenin-induced paw oedema is reduced in L-NA ME-treated rats, this response reflects a decrease in local blood flow rather than an effect on vascular permeability.