Thromboxane A2 antagonist inhibits leukotriene D4-induced smooth muscle contraction in guinea-pig lung parenchyma, but not in trachea.

Although the bronchoconstriction induced by leukotriene D4 (LTD4) has been reported to be partly mediated by thromboxane A2 (TXA2) in the guinea-pig airway, it is not known which part of the airway is susceptible to TXA2. In order to determine the role of TXA2 in the central and peripheral airways, we compared the effect of a TXA2 antagonist on tracheal strips to its effect on parenchymal strips of guinea-pigs. Tracheal and parenchymal strips were mounted in a 3.5 ml organ bath filled with Krebs-Henseleit solution aerated with 95% O2, 5% CO2 and kept at 37 degrees C. After equilibration for 60 min in Krebs solution, the strip was contracted by exposure to 10(-5) M of acetylcholine (ACh). Sixty minutes after ACh was eliminated, the concentration-response curve to LTD4 (10(-9) M-10(-7) M) was obtained, and the LTD4-induced contractions were expressed as the percent of the contraction evoked by 10(-5) M of ACh. We measured the contractile response to LTD4 in the presence or absence of the TXA2 antagonist, BAY u3405 (10(-8) M-10(-6) M). In the tracheal strips, BAY u3405 had no effect on the LTD4-induced contraction. However, in parenchymal strips, BAY u3405 significantly suppressed the contractile response to LTD4. These results suggest that in the central airway LTD4 contracts smooth muscle directly, but that in the peripheral airway LTD4 induces smooth muscle contraction both directly and indirectly, via TXA2.