Effects of indomethacin on the guinea-pig pulmonary response to intravenous leukotrienes C4 and D4.

We measured pulmonary conductance (GL), dynamic compliance (Cdyn.), and arterial pressure in chloralose-urethane anaesthetized guinea pigs for 30 min after intravenous infusion of either leukotriene (LT) C4 (1 microgram/kg) or LTD4 (0.5 microgram/kg) to control or indomethacin-pretreated (30 mg/kg) animals. LT infusion to control animals caused decrements in GL, which were maximal at 30 s and persisted for 7.5 min (LTD4) and 15 min (LTC4), decrements in Cdyn., which were maximal at 30 s and persisted for 30 min, and hypotension. Indomethacin treatment before LT infusion significantly altered the changes in GL by reducing the early (less than 1 min) response and potentiating the later (3-5 min) response, significantly reduced the fall in Cdyn. at all time points, resulting in a change in the GL/Cdyn. ratio to 1.0 and prolonged the hypotensive response. We conclude that cyclo-oxygenase products are responsible for the early (less than 1 min) pulmonary response to LT infusion and modulate the later (3-5 min) response but do not cause hypotension. With cyclo-oxygenase inhibition, the significant primary activity of LT is possibly less preferentially directed to contractile tissues associated with small airways.