Effects of Indomethacin on the Guinea-Pig Pulmonary Response to Intravenous Leukotrienes C4 and D4
- 1 September 1983
- journal article
- research article
- Published by Portland Press Ltd. in Clinical Science
- Vol. 65 (3) , 281-287
- https://doi.org/10.1042/cs0650281
Abstract
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.Keywords
This publication has 14 references indexed in Scilit:
- Contractile activities of leukotrienes C4 and D4 on vascular strips from rabbitsLife Sciences, 1981
- Bronchospasm and pressor effects induced in the guinea-pig by leukotriene C4 are probably due to release of cyclooxygenase productsEuropean Journal of Pharmacology, 1981
- Leukotriene-C4 induces generation of PGI2 and TXA2 in guinea-pig in vivoPharmacological Research Communications, 1981
- The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and ratProstaglandins, 1981
- Identification of the C(6)-S-conjugate of leukotriene a with cysteine as a naturally occurring slow reacting substance of anaphylaxis (SRS-A). Importance of the 11-cis-geometry for biological activityBiochemical and Biophysical Research Communications, 1980
- Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro.Proceedings of the National Academy of Sciences, 1980
- Slow reacting substances of anaphylaxis: Identification of leukotrienes C-1 and D from human and rat sourcesProceedings of the National Academy of Sciences, 1980
- Leukotriene C: a slow-reacting substance from murine mastocytoma cells.Proceedings of the National Academy of Sciences, 1979
- Resolution of prostaglandin endoperoxide synthase and thromboxane synthase of human platelets.Proceedings of the National Academy of Sciences, 1977
- The release of histamine and formation of a slow‐reacting substance (SRS‐A) during anaphylactic shockThe Journal of Physiology, 1960