Differing mechanisms for leukotriene d4-induced bronchoconstriction in guinea pigs following intravenous and aerosol administration.

Leukotriene D4 (LTD4) when administered intravenously or by aerosol to guinea pigs produced changes in pulmonary mechanics including a decrease in dynamic compliance and an increase in pulmonary resistance. The effects of intravenous LTD4 (0.5 microgram kg-1) were short lived and abolished by pretreatment of the animal with either cyclooxygenase inhibitors, a thromboxane synthetase inhibitor (OKY 1555) or an SRS-A antagonist (FPL 55712). These findings suggest that bronchoconstriction produced by the intravenous infusion of LTD4 at 0.5 microgram kg-1 is due to the release of thromboxane A2. However, in animals treated with indomethacin, LTD4 at higher doses (greater than 0.8 microgram kg-1) still elicited a bronchoconstriction which could be blocked by FPL 55712. Nebulization of 0.1 - 1.0 microgram of LTD4 into the lung produced prolonged changes in pulmonary mechanics which were inhibited by FPL 55712 and were potentiated by indomethacin. LTD4, therefore, when administered by aerosol produced effects on the lung which were not mediated by cyclooxygenase products. Responses to nebulized rather than intravenous LTD4 in the guinea pig may more closely resemble those seen in human tissues.