Role of kinins and nitric oxide on the rabbit arthritis induced by Bothrops jararaca venom

The effects of the nitric oxide synthase inhibitor N(omega)Nitro-L-arginine -methyl eater (L-NAME) and of the bradykinin B-2 receptor antagonist HOE 14 0 were evaluated in the inflammatory reaction induced by Bothrops jararaca venom (BjV) in New Zealand White rabbits. Arthritis was induced by injectin g 0.5 mi of a sterile solution of BjV (1-64 mu g/ml) into the knee intraart icular cavity. The contralateral joint was injected with bovine serum album in (BSA) diluted in sterile saline. At selected times thereafter (4, 24 and 48 h), the vascular permeability and the leukocyte influx in both the syno vial fluid and synovium were evaluated. BjV caused a dose-dependent increas e in both leukocyte influx and protein extravasation which reached a maxima l response at 16 mu g. Bothrops jararaca venom also induced the increase in the leukocyte accumulation in the synovium and in the concentration of bot h NO2/NO3 in the synovial fluid. Chronic administration of L-NAME (20 mg/kg /day in the drinking water for 2 weeks) markedly reduced the leukocyte accu mulation (90%), protein leakage (44%), and NO2/NO3 (50%) levels in the syno vial fluid, measured at the 4th h. Hoe 140, given i.v. (0.3 mg/kg, 30 min b efore) also reduced leukocyte accumulation (75%), protein leakage (48%), an d NO2/NO3 (79%) levels in the synovial fluid, measured at the 4th h. Simila r results were obtained with acute administration of L-NAME (30 mg/kg, i.v. , 30 min before). These results indicate that arthritis induced by BjV is t riggered by kinin formation and that the increase in both vascular permeabi lity and leukocyte accumulation is modulated by NO release. (C) 2000 Elsevi er Science Ltd. All rights reserved.