Cyclooxygenase mediated airway response to leukotriene D 4 in the cat

Abstract

The effects of leukotriene D 4 (LTD 4) on pulmonary mechanics were investigated in anesthetized, paralyzed cats under conditions of controlled ventilation. Intravenous injections of LTD 4 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). LTD 4 also increased systemic arterial pressure (P A0). The changes in P TP, R L, and C dyn in response to LTD 4 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 LTD 4 in increasing P TP, R L and decreasing C dyn in the cat. These data show that LTD 4 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 LTD 4 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.