BRADYKININ-INDUCED BRONCHOCONSTRICTION IN HUMANS - MODE OF ACTION

Abstract

The effect of bradykinin was studied by inhalation in normal and asthmatic human subjects, as well as on human bronchial smooth muscle in vitro. Bradykinin caused cough and retrosternal discomfort in all subjects and bronchoconstriction in asthmatic subjects. Bradykinin was approximately 10 times more potent than histamine and methacholine, and there was a significant correlation between the subjects'' sensitivity to histamine and bradykinin. Bradykinin-induced bronchoconstriction was prolonged when compared with that of histamine and the C-tiber stimulant capsaicin. This bronchoconstriction was subject to tachyphylaxis, which was also associated with desensitization of the subjects to inhaled histamine. The provocative dose causing a 35% fall in specific airway conductance (PD35) was unaffected by aspirin (1 g orally). However, ipratropium bromide (0.25 mg by nebulizer) significantly inhibited the effect of bradykinin, the PD35 being 0.8 .mu.mol (range, 0.16 to 3.4) and 0.15 .mu.mol (range, 0.047 to 1.15) after active dose and placebo, respectively (p < 0.05). Likewise, cromolyn sodium (40 mg dry powder) also significantly reduced response to bradykinin, with a PD35 of 0.04 .mu.mol (range, 0.13 to 0.31) after placebo and 0.39 .mu.mol (range, 0.05 to 4.45) after SCG (p < 0.05). Bradykinin only weakly constricted human bronchial smooth muscle in vitro. Bradykinin at 10-4 caused only 21.5 .+-. 5.5% of the maximal carbamylcholine contraction in 11 of 18 airways. Captopril did not enhance the effect of bradykinin. Bradykinin is a potent bronchoconstrictor of human airways in vivo, acting in part through cholinergic mechanisms but not because of the formation of prostaglandins.