Cysteinyl-leukotriene receptor antagonism blunts the acute hypotensive response to endotoxin in cats

Abstract

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.