Involvement of bradykinin B-1 and B-2 receptors in pulmonary leukocyte accumulation induced by Sephadex beads in guinea pigs

The effects of selected bradykinin receptor antagonists on leukocyte infilt ration into the lungs were studied in a model of guinea pig lung inflammati on induced by the intravenous injection of Sephadex beads. The bradykinin B -1 receptor antagonist, [Leu(8)]desArg(9)-BK (40 mg kg(-1) 24 h(-1)) and th e bradykinin B-2 receptor antagonist, DArg[Hyp(3),Thi(5),DTic(7),Oic(8)]BK (code name HOE 140; 4 mg kg(-1) 24 h(-1)), administered intravenously by os motic pumps, significantly reduced eosinophil counts by 33% and 42% in bron choalveolar fluid, respectively. HOE 140 decreased neutrophil counts by 35% . LysLys[Hyp(3),Igl(5),D-Igl(7),Oic(8)]desArg(9)BK (code name B 9858), a ne wly described bradykinin B, receptor antagonist, administered intraperitone ally (1 mg kg(-1)), decreased eosinophil and neutrophil counts by 45% in br onchoalveolar fluid. D-Arg[Hyp(3),Igl(5),D-Igl(7),Oic(8)]BK (code name B 94 30), a non-selective bradykinin B-1/B-2 receptor antagonist, also administe red intraperitoneally (1 mg kg(-1)), decreased eosinophil and macrophage co unts by 62% and 80% in bronchoalveolar fluid. These results suggest that br adykinin B-1 and B-2 receptors are involved in leukocyte recruitment in our model of lung inflammation. (C) 1999 Elsevier Science B.V. All rights rese rved.