Interrelationship of the Kinin System, Nitric Oxide and Eicosanoids in the Antigen‐Induced Arthritis in Rabbits

Abstract

The aim of the present study was to investigate the interrelationship of the kinin system, nitric oxide and eicosanoids in the acute phase of antigen-induced arthritis (AIA) in rabbits. The arthritis was induced in immunized rabbits and the following parameters were evaluated 24 hours later: leukocyte influx (total and differential white cell count), vascular permeability (Evans's blue method), and synovial PMN cell infiltrate. PGE2 and LTB4 (radioimmunoassay) levels were quantified in the synovial fluid. The animals were pre-treated with 20mg/kg/day during 14 days with L-NAME or D-NAME and/or Enalapril (0.12 mg/kg/day-14 days), and/or the B2 antagonist of Bradykinin HOE 140 (0.9 mg/kg). Our results showed that L-NAME was effective in the prevention of AIA with reduction of all Inflammatory parameters analyzed. Enalapril partially reverted the L-NAME anti-inflammatory effects. The simultaneous treatment with HOE 140 abolished this reversion and returned the inflammatory parameters to the levels observed in L-NAME treated animals. Our results suggest that pressoric alterations induced by L-NAME could not account for all its anti-inflammatory action in this model of experimental arthritis. Additionally the contribution of the kinin system in AIA was characterized as well as its interaction with eicosanoids and nitric oxide.

Chronic blockade of nitric oxide biosynthesis in rats: effect on leukocyte endothelial interaction and on leukocyte recruitment

“…We had already demonstrated that rabbits submitted to the same pharmacological treatment had reduction in cellular recruitment and vascular permeability on arthritis induced even by BjV or by serum albumin bovine [9,[30][31][32]. Additionally, the reduced inflammatory response observed in L-NAME treated rats is in agreement with other experimental studies which employed different schedules of treatments and stimulus [48 -51].…”

“…Previous studies demonstrated that in vitro incubation with NOS inhibitors attenuates subsequent chemotaxis of polymorphonuclear cells [52 -55]. It is important to note that this protocol of treatment also promoted reduction on IL1 and eicosanoids levels on inflammatory exudates, which may contribute to the impairment of the inflammatory reaction [9,30,32].…”

“…It has been demonstrated that in vivo non-specific pharmacological inhibition of nitric oxide synthases (NOS) reduces leukocyte migration to inflammatory sites promoting amelioration of pathological conditions [1 -8]. The reduction is not likely to depend on the hypertensive effect evoked by these inhibitors, because pharmacological normalisation of blood pressure does not prevent the decrease in the number of leukocytes migrating to the inflamed area [9].…”

“…We have previously shown that chronicle L-NAME treatment (14 days, 20 mg/kg, oral route) reduces albumin leakage and leukocyte migration to the articular cavity of rabbits in which an arthritic lesion was induced, either immunologically or by the injection of Bothrops jararaca venom (BjV) [9,30,31]. The efficacy of NO synthesis blockade was confirmed by a significant reduction in levels of NO metabolites (nitrate/nitrite) in the synovial fluid [9, 30 -32].…”

Systemic Macrophage Activation in Locally-induced Experimental Arthritis

“…The lack of NO in the AIA joints, on the other hand, represents a clear difference in comparison with human RA [4] and experimental arthritides, such as AIA in rabbits [34] and rats [20]. Since the presence of inhibitors of the NO detection assay was excluded, the present findings probably reflect species differences in the AIA model.…”