Suppressive effect of distinct bradykinin B2 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 mediating 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 by 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, including early protein exudation and neutrophilia and late pleural eosinophil 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 pleural plasma leakage, neutrophil accumulation and late eosinophil influx. 4 Moreover, the B-2 receptor antagonists also dose-dependently inhibited the allergic like inflammatory pleurisy triggered by bradykinin (50 mu g cavity(-1)), which is characterized by acute mast cell degranulation, protein leakage 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 allergic mast cell-dependent inflammation in rats, and suggest that B-2 receptor antagonists may be useful therapeutically to control allergic dysfunction.