Effect of leukotrienes on sheep airway smooth muscle

The effects of leukotrienes (LT) C4, LTD4, LTE4 and LTB4 on the development of isometric tension by sheep airway smooth muscle were determined in a tissue bath. LTE4 (1.5 x 10(-7) M) had no contractile effect. LTB4 contracted only lung parenchymal strips. LTC4 (8 x 10(-8) M) and LTD4 (1.1 x 10(-7) M) caused contractions in trachea, bronchi and lung parenchyma that developed slowly and persisted. The tracheal contractions caused by LTD4 and ACh were potentiated approx. 30% by the cyclooxygenase inhibitor meclofenamate (10(-6) M). Meclofenamate had no effect on leukotriene induced contractions in bronchi or lung parenchymal strips. The bronchodilator prostaglandins PGI2 and PGE2 were released from sheep trachea at rest and after contraction by LTD4. Inhibition of their release by meclofenamate may explain the potentiation of LTD4 contractions by meclofenamate. In vitro, LTD4 and LTC4 have potent contractile effects on sheep airway smooth muscle that are not mediated by the secondary release of constrictor cyclooxygenase products. These leukotrienes may play a substantial role in the pathogenesis of allergen and endotoxin induced lung mechanics changes in sheep.