Inhibitory effect of a thromboxane A2 synthetase inhibitor OKY-046 on bronchial hyperresponsiveness to histamine, but not on airway wall thickening, induced by intravenous administration of leukotriene C4 in guinea-pigs.

We studied the effect of i.v.administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea-pigs. The infusion of 3 micrograms/kg LTC4 for 1 h induced an increase of the relative thickness of the airway wall in peripheral bronchi, found by histological examination. In analysis of airway function, the infusion of 3 micrograms/kg LTC4 for 1 h induced airway wall thickening and airway hyperresponsiveness to histamine administered i.v.at doses of 1.8 and 3.6 micrograms/kg. Thromboxane A2 synthetase inhibitor OKY-046, which was administered perorally, inhibited the LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner at doses from 30-100 mg/kg, but not the airway wall thickening induced by LTC4.