Suppressive effect of distinct bradykinin B-2 receptor antagonist on allergen-evoked exudation and leukocyte infiltration in sensitized rats

1 Bradykinin is suggested to play a role in the pathophysiology of several acute and chronic diseases, including allergic disorders such as asthma. In the present study, we have investigated the importance of bradykinin in me diating allergic inflammation in rats. 2 To this end we have tested the effects of the Bz receptor antagonists Hoe 140, FR173657 or FR172357 on the pleural inflammatory response triggered b y intrapleural (i.pl.) injection of allergen (ovalbumin, 12 mu g cavity(-1) ) in 14 day-actively sensitized Wistar rats. Analysis of the pleural fluid effluent revealed a sequence of mast cell-dependent inflammatory events, in cluding early protein exudation and neutrophilia and late pleural eosinophi l influx. 3 Local treatment with Hoe 140 (0.1 and 1 mu g cavity(-1)), FR173657 (1 and 10 mu g cavity(-1)) or FR172357 (1 and 10 mu g cavity(-1)) inhibited dose- dependently allergen-induced mast cell activation with impairment of pleura l plasma leakage, neutrophil accumulation and late eosinophil influx. 4 Moreover, the B-2 receptor antagonists also dose-dependently inhibited th e allergic like inflammatory pleurisy triggered by bradykinin (50 mu g cavi ty(-1)), which is characterized by acute mast cell degranulation, protein l eakage and pleural eosinophil infiltration. 5 Taken together, our findings provide substantial evidence to suggest that bradykinin acting on its B-2 receptors play a critical role in mediating a llergic mast cell-dependent inflammation in rats, and suggest that B-2 rece ptor antagonists may be useful therapeutically to control allergic dysfunct ion.