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

ABSTRACT

The effects of the nitric oxide synthase inhibitor N(omega)Nitro-L-arginine-methyl ester (L-NAME) and of the bradykinin B(2) receptor antagonist HOE 140 were evaluated in the inflammatory reaction induced by Bothrops jararaca venom (BjV) in New Zealand White rabbits. Arthritis was induced by injecting 0.5 ml of a sterile solution of BjV (1-64 microg/ml) into the knee intraarticular cavity. The contralateral joint was injected with bovine serum albumin (BSA) diluted in sterile saline. At selected times thereafter (4, 24 and 48 h), the vascular permeability and the leukocyte influx in both the synovial fluid and synovium were evaluated. BjV caused a dose-dependent increase in both leukocyte influx and protein extravasation which reached a maximal response at 16 microg. Bothrops jararaca venom also induced the increase in the leukocyte accumulation in the synovium and in the concentration of both NO(2)/NO(3) in the synovial fluid. Chronic administration of L-NAME (20 mg/kg/day in the drinking water for 2 weeks) markedly reduced the leukocyte accumulation (90%), protein leakage (44%), and NO(2)/NO(3) (50%) levels in the synovial fluid, measured at the 4th h. Hoe 140, given i.v. (0.3 mg/kg, 30 min before) also reduced leukocyte accumulation (75%), protein leakage (48%), and NO(2)/NO(3) (79%) levels in the synovial fluid, measured at the 4th h. Similar 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 triggered by kinin formation and that the increase in both vascular permeability and leukocyte accumulation is modulated by NO release.