1. 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 μg/kg) or LTD4(0.5 μg/kg) to control or indomethacin-pretreated (30 mg/kg) animals.
2. 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.
3. Indomethacin treatment before LT infusion significantly altered the changes in GL by reducing the early (< 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.
4. We conclude that cyclo-oxygenase products are responsible for the early (< 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.