Effects of a thromboxane antagonist (BM 13.177) during endotoxin-induced pulmonary vasoconstriction in sheep.
We investigated the effect of a thromboxane antagonist, BM 13.177, during endotoxin-induced pulmonary vasoconstriction in sheep. In control animals intravenous E-coli endotoxin (1 microgram/kg) caused a transient increase of pulmonary artery and airway pressure paralleled by large concentration increases of TXB2: in comparison peak plasma concentrations of 6-keto-PGF1 alpha (a prostacyclin metabolite) were small and delayed in time. Pre-treatment with BM 13.177 (bolus 5 mg/kg), followed by 0.75 mg/kg/min intravenously) abolished the rise of pulmonary artery and airway pressure. Plasma concentrations of TXB2 and 6-keto-PGF1 alpha were similar to controls. These and previous investigations imply that BM 13.177 specifically antagonizes TXA2 on the putative receptor in pulmonary vascular and airway smooth muscle.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D008168:Lung / Q000098:blood supply; D012756:Sheep; D013449:Sulfonamides / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
D004731:Endotoxins; D013449:Sulfonamides; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C040624:sulotroban