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 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.
Bandeira-Melo
C
C
Department of Physiology and Pharmacodynamics, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Calheiros
A S
AS
Silva
P M
PM
Cordeiro
R S
RS
Teixeira
M M
MM
Martins
M A
MA
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D015550:Cell Degranulation / Q000187:drug effects; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D010998:Pleurisy / Q000276:immunology / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D043782:Receptor, Bradykinin B2; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000485:Allergens; D018926:Anti-Allergic Agents; D065168:Bradykinin Receptor Antagonists; C105311:FR 173657; D010972:Platelet Activating Factor; D011506:Proteins; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D003189:p-Methoxy-N-methylphenethylamine; C065679:icatibant; D001920:Bradykinin