CONTRACTILE EFFECTS OF BRADYKININ ON THE ISOLATED HUMAN SMALL BRONCHUS

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD(2) was 7.7 +/- 0.1 (pD(2) = -log EC(50)) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B-2 agonist [Hyp(3)TyrMe(8)]Bk contracted airway smooth muscle with a pD(2) of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B-2 agonist [Sar(1)dPhe(8)desArg(9)]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B-2 (Hoe 140) but not by the B-1 [Leu(8)desArg(9)]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action, Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin, (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B-2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.