Implication of the bradykinin receptors in antigen‐induced pulmonary inflammation in mice

The involvement of bradykinin (BK) receptors in the allergic inflammation associated with airway hyper‐reactivity (AHR) was evaluated by means of the selective bradykinin B 1 receptor (BKB 1 ‐R) antagonists R‐715 (Ac‐Lys‐[ D ‐ β Nal 7 , Ile 8 ]desArg 9 ‐BK) and R‐954 (Ac‐Orn[Oic 2 , α ‐MePhe 5 , D ‐ β Nal 7 , Ile 8 ]desArg 9 ‐BK) or the selective bradykinin B 2 receptor (BKB 2 ‐R) antagonist HOE‐140 ( D ‐Arg 0 ‐Hyp 3 ‐Thi 5 ‐D‐Tic 7 ‐Oic 8 ‐BK). Cellular migration and AHR were examined 24 h after the second ovalbumin (OA) challenge. R‐715 (10–500 μ g kg −1 ) and R‐954 (1–100 μ g kg −1 ) injected intravenously (i.v.), 5 min prior to aerosol OA challenges, decreased by approximately 50% the induced lung eosinophilia in OA‐sensitized mice but did not reduce AHR. HOE‐140 (1 μ g kg −1 ) administered in the same manner, decreased mononuclear cell and eosinophil infiltration in the bronchoalveolar lavage fluid (BALF) of OA‐sensitized mice. Moreover, treatment of OA‐sensitized mice with HOE‐140 (100 μ g kg −1 ) completely abolished the AHR to carbachol. The BKB 1 ‐R agonist desArg 9 ‐BK (DBK; 10–1000 μ g kg −1 ) administered intratrachealy to normal mice had no effect on the basal cell counts recovered in BALF nor on the plasma extravasation, while the BKB 2 ‐R selective agonist BK (20 μ g kg −1 ) stimulated mononuclear cell migration, neutrophilia and plasma extravasation in normal mouse lungs. Such effects were inhibited by HOE‐140 (10 μ g kg −1 ). Our results suggest that the airway inflammatory response induced by antigen challenge in mice is mediated by stimulation of both BKB 1 ‐R and BKB 2 ‐R.British Journal of Pharmacology (2003) 138 , 1589–1597. doi: 10.1038/sj.bjp.0705207