title: Leukotriene E4 causes pulmonary vasoconstriction, not inhibited by meclofenamate.
abstract: Leukotriene E4 (LTE4) appears to be a rather stable product of the lipoxygenase pathway. Its action in the pulmonary circulation is unknown. Therefore we investigated its effect on the circulation of isolated rat lungs perfused with a cell- and plasma-free solution. Synthetic LTE4 in doses from .15 micrograms to 5 micrograms/.25 ml .9% NaCl injected as a bolus in the pulmonary artery during normoxia caused a fast, transient perfusion pressure increase within seconds. This was followed by a slow rise in baseline perfusion pressure (normoxia) over 25 min. In addition, 5 micrograms LTE4 caused edematogenic lung damage. Injection of 1.5 micrograms LTE4 during hypoxic vasoconstriction caused fast, transient pressure rises, similar to normoxic conditions. 6-keto-PGF1 alpha and TXB2 were measured in the lung effluent before and after LTE4 injection. Neither 6-keto-PGF1 alpha nor TXB2 production changed after LTE4 injection. Meclofenamate (.5 micrograms/ml) increased the fast, transient and the slow, sustained pressure rise. We conclude that LTE4 caused direct pulmonary vasoconstriction unrelated to cyclooxygenase products.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D007545:Isoproterenol / Q000494:pharmacology; D017999:Leukotriene E4; D008168:Lung / Q000098:blood supply*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D013189:SRS-A; D062367:ortho-Aminobenzoates; D008469:Meclofenamic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D017999:Leukotriene E4; D007545:Isoproterenol