Contribution of B 2 receptors for bradykinin in Arthus reaction‐induced plasma extravasation in wild‐type or B 2 transgenic knockout mice

The aim of the present study was to investigate the contribution of bradykinin (BK) B 1 and B 2 receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wild‐type mice and transgenic B 2 knockout littermates. BK (10 μg mouse −1 ) or bovine serum albumin (0.5 mg mouse −1 ) induced a sustained Evans blue extravasation for more than 80 min in naive or rabbit anti‐bovine serum albumin‐treated mice (RPA model), respectively. The response to the two stimuli was prevented by the B 2 receptor antagonist, HOE‐140, but not by [Leu 8 ]desArg 9 ‐BK (B 1 receptor antagonist). In contrast to the wild‐type littermates, RPA and bradykinin were unable to trigger an increase in plasma extravasation in B 2 knockout mice. Furthermore, endothelin‐1 (5 μg mouse −1 ) and a selective NK‐1 receptor agonist [Sar 9 ,Met (O 2 ) 11 ]‐SP (20 μg mouse −1 ), triggered a significant increase in peritoneal plasma extravasation in both wild‐type and B 2 knockout animals. A pretreatment with indomethacin (200 μg mouse −1 ) significantly reduced the RPA‐induced but not the BK‐induced increase in Evans blue extravasation. Furthermore, RPA, but not BK, triggered a significant indomethacin‐sensitive increase in peritoneal prostaglandin E 2 content. Our results suggest a pivotal role for B 2 receptors in the mechanism of plasma extravasation which occurs during the reverse passive Arthus reaction in the mouse. Moreover, our results suggest an important contribution of prostanoids in the plasma leakage mechanisms triggered by RPA but not by bradykinin. British Journal of Pharmacology (2000) 129 , 1732–1738; doi: 10.1038/sj.bjp.0703225