ROLE OF THROMBOXANE A(2) IN BRADYKININ-INDUCED HUMAN ISOLATED SMALL BRONCHI CONTRACTION

We previously demonstrated that the bradykinin-induced contraction of human isolated small bronchi is inhibited by indomethacin, capsaicin ( N-methyl-N-6-nonenamide) and ruthenium red but not by tachykinin recep tor antagonists. The thromboxane A(2) receptor (TP receptor) antagonis t GR32191 ((1R-(1 alpha(Z),2 beta,3 beta,5 )-methoxy)hydroxy-2-(1-pipe ridinyl)cyclopentyl)-4- acid, hydrochloride) (10(-10) to 10(-8) M) dos e dependently inhibited the effect of bradykinin, suggesting the media tion of the TP receptor in the action of bradykinin. With higher conce ntrations of GR32191 (10(-7) and 10(-6) M) bradykinin induced a relaxa tion which was inhibited by indomethacin and by the bradykinin B-2, re ceptor antagonist Hoe 140 (D-ArgO[Hyp(3),Thi(.5),-Tic(7),Oic(8)]bradyk inin. The thromboxane A(2) synthase inhibitor dazoxiben (4-(-2-(1H-imi dazol-1-yl)ethoxy) benzoic acid hydrochloride) 10(-6) M inhibited the bradykinin-induced contraction, suggesting that thromboxane A(2) was i nvolved in TP receptor stimulation. The thromboxane A(2) mimetic U-466 19 (9,11-dideoxy-11 alpha,9 alpha-epoxymethano-prostaglandin F-2 alpha )-induced contraction of human distal bronchi was not inhibited by cap saicin and ruthenium red. Our data suggest that bradykinin contracts h uman isolated small bronchi through thromboxane A(2) release. The inhi bitory effect of ruthenium red and capsaicin on the bradykinin respons e may be due to inhibition of thromboxane A(2) release or arachidonic mobilisation.