Cyclooxygenase mediated airway response to leukotriene D4 in the cat

The effects of leukotriene D₄ (LTD₄) on pulmonary mechanics were investigated in anesthetized, paralyzed cats under conditions of controlled ventilation. Intravenous injections of LTD₄ in doses of 3, 10, and 30 μg caused significant increases in transpulmonary pressure (P_TP) and lung resistance (R_L) while decreasing dynamic compliance (C_dyn). LTD₄ also increased systemic arterial pressure (P_A0). The changes in P_TP, R_L, and C_dyn in response to LTD₄ were blocked by sodium meclofenamate, a cyclooxygenase inhibitor. However, there was no significant change in the increase in P_A0 following cyclooxygenase blockade. U 46619, a thromboxane mimic, was 30 to 100 times more potent than LTD₄ in increasing P_TP, R_L and decreasing C_dyn in the cat. These data show that LTD₄ has significant smooth muscle constrictor activity in central airways as well as peripheral portions of the feline lung. In addition, these data suggest that in the cat the actions of intravenously administered LTD₄ on lung mechanics are mediated by release of cyclooxygenase products while the systemic pressor effects are not dependent upon the integrity of the cyclooxygenase pathway.