The response of isolated human bronchial muscle preparations to leukotriene D4 (LTD4, 0.1 microM; 0.22 +/- 0.03 g/mm2) was similar to that of histamine (50 microM; 0.21 +/- 0.02 g/mm2). Isolated pulmonary venous preparations also contracted to these same concentrations of both agonists (LTD4, 0.32 +/- 0.19 g/mm2; and histamine, 0.36 +/- 0.07 g/mm2). However, pulmonary arterial preparations responded to histamine (50 microM, 0.59 +/- 0.10 g/mm2) but exhibited a reduced response to LTD4 (0.3 microM, 0.06 +/- 0.01 g/mm2). Bronchial and pulmonary venous muscle preparations from the human lung had the same sensitivities to LTD4 (pD2 values: bronchus, 7.95 +/- 0.08 and vein, 7.76 +/- 0.07). When bronchial or pulmonary venous muscle preparations were incubated for 30 min with either diltiazem (10 microM), indomethacin (1.7 microM) or L-cysteine (3 microM), the LTD4 cumulative concentration-effect curves following these drug treatments were similar to controls. However, FPL-55712 (10 microM) significantly shifted the LTD4 concentration-effect curves produced in bronchial preparations to the right. In isolated pulmonary arterial preparations none of these drug treatments enhanced the LTD4 response. These results show that isolated human pulmonary arterial preparations are less responsive to LTD4 than bronchial or venous preparations. In addition, the data obtained subsequent to the various drug treatments indirectly suggest that the LTD4 contraction is not modified by a calcium channel blocker or by inhibition of the endogenous products of the cyclooxygenase pathway.

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Human isolated lung preparations were passively sensitized using mouse monoclonal dinitrophenyl (DNP)-specific IgE antibodies. The contractile response to antigen (DNP-bovine serum albumin; DNP-BSA) was approximately 80% of the histamine response (50 µM: 0.20 ± 0.03 g/mm²) in bronchial muscle preparations. In passively sensitized pulmonary vascular and parenchymal preparations, the contraction to antigen was negligible. Indomethacin (1.7 µM; 30 min) did not alter the contractile response to DNP-BSA (5 µg/ml) in bronchial tissues. In passively sensitized bronchial muscle preparations stimulated with DNP-BSA, there was a significant increase (2-fold) in prostanoid production. This production was inhibited by indomethacin. These data suggest that endogenous prostaglandins may not play a role in the regulation of human isolated bronchial muscle contraction to antigen in vitro.