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.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001696:Biomechanical Phenomena; D001794:Blood Pressure / Q000187:drug effects; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D013189:SRS-A / Q000494:pharmacology*; D013997:Time Factors
D013189:SRS-A; D007213:Indomethacin