Inhibition by thromboxane antagonists of airway hyperresponsiveness to histamine induced by 13,14-dihydro-15-keto-PGF in guinea-pigs


Dr M. Kurosawa, First Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Shyowa-machi, Maebashi 371, Japan.


Summary. We studied the effect of intravenous administration of 13,14-dihydro-15-keto-prostaglandin (PG) F27alpha; on airway responsiveness to histamine and airway wall thickening in guinea-pigs. Guinea-pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded sections of the lungs were stained and the airways that were cut in transverse section were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous administration of histamine before and after the intravenous administration of 13,14-dihydro-l5-keto-PGF2n. Intravenous administration of 10/μg/kg 13,14-dihydro-15-keto-PGF for 1 h did not induce an increase of the relative thickness of the airway wall by the histological examination. In analysis of airway function, intravenous administration of 10μg/kg 13,14-dihydro-15-keto-PGF for 1 h induced airway hyperresponsiveness to histamine without airway wall thickening. Thromboxane A2 (TXA2) receptor antagonists ONO-NT-126 and ONO-8809 inhibited the 13,14-dihydro-15-keto-PGF-induced airway hyperresponsiveness to histamine, suggesting that the effect of 13,14-dihydro-15-keto-PGF on bronchial hyperresponsiveness is likely to be mediated through TXA2.