PHARMACOLOGY AND MODE OF ACTION OF BRADYKININ ON MOUSE-ISOLATED TRACHEA

In the present study, the effect of bradykinin on basal and precontrac ted mouse-isolated trachea was investigated. In basal conditions mouse -isolated tracheal rings do not respond to bradykinin. However, when t he tracheal rings were precontracted with carbachol (10(-7) M) a relax ation with bradykinin 13.10(-9)-3.10(-7) was found. The maximal respon se amounted 69.7+/-4.1% (n=15) with a pD(2) value of 7.21+/-0.21. The selective bradykinin B-2 receptor antagonist HOE 140 (10(-10)-10(-8) M ) antagonized the bradykinin-induced relaxation, while the bradykinin B-1 receptor antagonist des-Arg(9)-Leu(8)-bradykinin (10(-6) M) had no influence. The selective bradykinin B-1 receptor agonist des-Arg(9)-b radykinin (10(-6) M) caused a small relaxation (8.4+/-2.5%, n=6), whic h could be antagonized completely by the selective bradykinin B-1 rece ptor antagonist des-Arg(9)-Leu(8)-bradykinin (10(-6) M) while addition of the selective bradykinin B-2 receptor antagonist HOE 140 (10(-8) M ) was without effect. In the presence of indomethacin (10(-6) M) the r elaxation of bradykinin was completely abolished. Pretreatment of the tracheal rings with capsaicin, or the presence of the selective NK1 re ceptor antagonist RP 67851 (10(-6) M) or the presence of the nitric ox ide synthase inhibitor L-NAME (3.10(-4) M) had no effect on the bradyk inin-induced relaxation. In conclusion, these results demonstrate that the mouse-isolated tracheal is a preparation in which bradykinin exer ts a relaxant response via stimulation of bradykinin B-2 receptors. Th is response is probably mediated by prostaglandines.