[Effect of thromboxane A2 (TXA2) antagonists on bronchial hyperresponsiveness induced by intravenous administration of leukotriene C4 (LTC4) in guinea pigs]

Abstract

Effects of TXA2 antagonists on bronchial hyperresponsiveness induced by intravenous administration of LTC4 in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance, using a formula to exclude the effects of changes in airway wall thickness. With the formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness to histamine. Administration of LTC4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was enhanced by the administration of LTC4. TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the increased ratio of bronchial smooth muscle constriction of LTC4. On the other hand, the antagonists showed no significant effects on airway wall edema by LTC4. These results suggest TXA2 may play a role in LTC4-induced bronchial hyperresponsiveness to histamine.