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 B2 receptor antagonists
Hoe 140,
FR173657 or FR172357 on the pleural inflammatory response triggered by intrapleural (i.pl.) injection of
allergen (
ovalbumin, 12 microg 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 microg cavity(-1)),
FR173657 (1 and 10 microg cavity(-1)) or FR172357 (1 and 10 microg 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 B2 receptor antagonists also dose-dependently inhibited the allergic like inflammatory
pleurisy triggered by
bradykinin (50 microg 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 B2 receptors play a critical role in mediating allergic mast cell-dependent
inflammation in rats, and suggest that B2 receptor antagonists may be useful therapeutically to control allergic dysfunction.