Leukotriene D₄ increases pulmonary vascular permeability and pressure by different mechanisms in the rabbit

We designed experiments to define the effects of leukotriene D₄ (LTD₄) in the rabbit lung and to determine whether or not these effects were due to the synthesis of cyclooxygenase products. Infusion of LTD₄ (0.01, 0.03, and 0.10 μg) into the rabbit pulmonary vasculature caused a dose-related increase in pulmonary arterial pressure and tracheal pressure. Pretreatment with FPL 55712 (38 μM), a leukotriene receptor antagonist, or indomethacin (10 μg/ml of perfusate) completely prevented the increase in tracheal and pulmonary arterial pressure. We also studied the effect of LTD₄ on pulmonary vascular permeability by measuring lung weight gain at 4 levels of left atrial pressures (0, 5, 10, and 15 mmHg). Leukotriene D₄ increased lung weight gain at all levels of left atrial pressure compared with that in the control group. Pretreatment with FPL 55712 completely inhibited the increase in vascular permeability caused by LTD₄. Although pretreatment with indomethacin blocked the increase in tracheal and vascular pressure caused by LTD₄, it did not prevent the increase in vascular permeability. We conclude that in the rabbit, LTD₄ increases tracheal pressure, pulmonary arterial pressure, and pulmonary vascular permeability. Leukotriene D₄ increases tracheal and pulmonary arterial pressure by stimulating the synthesis of cyclooxygenase products, and it increases vascular permeability through a mechanism that does not require the synthesis of cyclooxygenase products.