Inhibition of 9 alpha,11 beta-prostaglandin F2-induced bronchial hyperresponsiveness by thromboxane A2 receptor antagonists in guinea pigs.

We studied the effect of intravenous administration of 9 alpha,11 beta-prostaglandin F2 on bronchial responsiveness to histamine and airway wall thickening in guinea pigs. The infusion of 9 alpha,11 beta-prostaglandin F2 induced an increase of the relative thickness of the airway wall in peripheral bronchi demonstrable by histological examination. Analysis of airway function showed that the infusion of 9 alpha,11 beta-prostaglandin F2 induced airway hyperresponsiveness to histamine with airway wall thickening. The thromboxane A2 receptor antagonists, ONO-NT-126 (5(Z)-6-[(1R,2R,3R,4S)-3-(n-4-bromobenzenesulfonyl-aminomethyl) bicyclo[2.2.1]heptane-2-yl]hex-5-enoic acid) and ONO-8809 (n-decyl(Z)-6-[(1S,2S,3R,4R)-3-(4-bromobenzenesulfonylaminomethyl) bicyclo[2.2.1]hept-2-yl]-5-hexenoate), inhibited these effects of 9 alpha,11 beta-prostaglandin F2 in a dose-dependent manner.