Leukotriene (LT) has been suggested to play an important role in the pathogenesis of bronchial asthma. In the present study, the effects of intravenous administration of LTC4 and LTD4 on bronchial smooth muscle in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance using a formula that excludes the effect of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of LTC4 and LTD4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of LTC4 and LTD4. Moreover, the LT antagonist ONO-1078 inhibited the effect of LTC4 and LTD4 administration. These results suggest that LTC4 and LTD4 can be important mediators affecting bronchial hyperresponsiveness.
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