Leukotriene antagonist FPL 57231 prevents the acute pulmonary effects of Escherichia coli endotoxin in cats.
We studied the effects of a selective leukotriene (LT) antagonist (FPL 57231, 2 mg kg-1 min-1) on the acute cardiopulmonary changes observed in feline endotoxin shock. LTC4 and LTD4 (0.1-3.0 micrograms kg-1) given intravenously had little or no activity on pulmonary arterial pressure (PAP), dynamic lung compliance (Cdyn), and airways resistance (Raw). They did, however, produce a systemic hypertension, which was significantly attenuated during the FPL 57231 infusion. E. coli endotoxin (2 mg kg-1) administration resulted in decreases in systemic arterial blood pressure and Cdyn, together with increases in both PAP and Raw. During infusion of FPL 57231, all these endotoxin-induced cardiopulmonary changes were attenuated. Radioimmunoassay of blood samples taken from cats given FPL 57231 showed that levels of 6-keto prosta-glandin F1 alpha and thromboxane B2 were not significantly increased by endotoxin, as would normally be expected in cats administered endotoxin. FPL 57231 was also found to antagonise the pulmonary effects of the thromboxanemimetic U46619 and of prostaglandin F2 alpha. These results indicate that it is unlikely that the leukotrienes are involved as important mediators of the acute phase of endotoxin shock in cats.
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002867:Chromones / Q000008:administration & dosage / Q000627:therapeutic use*; D015237:Dinoprost; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli; D005069:Evaluation Studies as Topic; D006976:Hypertension, Pulmonary / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D011449:Prostaglandin Endoperoxides / Q000037:antagonists & inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D011460:Prostaglandins F / Q000037:antagonists & inhibitors; D011652:Pulmonary Circulation / Q000187:drug effects; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012772:Shock, Septic / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000097:blood
D002867:Chromones; D004731:Endotoxins; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011460:Prostaglandins F; D013189:SRS-A; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C034338:FPL 57231; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost