Cysteinyl-leukotriene receptor antagonism blunts the acute hypotensive response to endotoxin in cats.
This study evaluated the effects of a cysteinyl-leukotriene-1 (cys-LT(1)) receptor antagonist, zarfirlukast, during feline endotoxemia. Six adult, sexually intact male cats received either placebo or zarfirlukast (10mg, PO) and endotoxin (2 μg/kg/h q 6h) in a cross-over design. Rectal temperature, heart rate, systolic arterial blood pressure, plasma tumor necrosis factor (TNF) activity, interleukin (IL)-6 concentration and urine cys-LT to creatinine ratio were evaluated. The rectal temperature, plasma TNF activity and IL-6 concentrations were significantly higher and systolic arterial blood pressure and heart rate significantly lower after endotoxin infusion. Cats treated with zafirlukast had a significantly higher blood pressure at 4h (P=0.002) compared to placebo. Urine cys-LT to creatinine ratio was significantly greater in the cats treated with zafirlukast compared to placebo (P=0.02). Zafirlukast administration ameliorated the acute hypotensive response to endotoxin in cats, but failed to significantly alter rectal temperature, heart rate or production of TNF and IL-6.
DeClue
Amy E
AE
Department of Medicine and Surgery, College of Veterinary Medicine, University of Missouri, 900 E Campus Drive, Columbia, MO 65211, USA. decluea@missouri.edu
Sharp
Claire R
CR
Cohen
Rachael L
RL
Leverenz
Elizabeth F
EF
Reinero
Carol R
CR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature; D002371:Cat Diseases / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D002415:Cats; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D003545:Cysteine / Q000652:urine; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy / Q000652:urine / Q000662:veterinary*; D004731:Endotoxins / Q000008:administration & dosage; D006339:Heart Rate; D007022:Hypotension / Q000517:prevention & control / Q000662:veterinary*; D007211:Indoles; D015850:Interleukin-6 / Q000032:analysis; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D015289:Leukotrienes / Q000652:urine; D008297:Male; D048448:Phenylcarbamates; D018077:Receptors, Leukotriene / Q000187:drug effects*; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004731:Endotoxins; D007211:Indoles; D015850:Interleukin-6; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D048448:Phenylcarbamates; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014105:Tosyl Compounds; D014409:Tumor Necrosis Factor-alpha; C112381:cysteinyl-leukotriene; D003404:Creatinine; D003545:Cysteine; C083169:leukotriene D4 receptor; C062735:zafirlukast