INHIBITION BY THROMBOXANE ANTAGONISTS OF AIRWAY HYPERRESPONSIVENESS TO HISTAMINE-INDUCED BY 13,14-DIHYDRO-15-KETO-PGF(2-ALPHA) IN GUINEA-PIGS

We studied the effect of intravenous administration of 13,14-dihydro-1 5-keto-prostaglandin (PG) F-2 alpha on airway responsiveness to histam ine and airway wall thickening in guinea-pigs. Guinea-pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded s ections of the lungs were stained and the airways that were cut in tra nsverse section were measured by tracing enlarged images using a digit izer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway w all thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous admin istration of histamine before and after the intravenous administration of 13,14-dihydro-15-keto-PGF(2 alpha). Intravenous administration of 10 mu g/kg 13,14-dihydro-15-keto-PGF(2 alpha) for 1 h did not induce a n increase of the relative thickness of the airway wall by the histolo gical examination. In analysis of airway function, intravenous adminis tration of 10 mu g/kg 13,14-dihydro-15-keto-PGF(2 alpha) for 1 h induc ed airway hyperresponsiveness to histamine without airway wall thicken ing. Thromboxane A(2) (TXA(2)) receptor antagonists ONO-NT-126 and ONO -8809 inhibited the 13,14-dihydro-15-keto-PGF(2 alpha)-induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14- dihydro-15-keto-PGF(2 alpha) on bronchial hyperresponsiveness is likel y to be mediated through TXA(2).