Beneficial effects of a leukotriene antagonist on endotoxin-induced acute hemodynamic alterations.
The role of lipoxygenase metabolites of arachidonic acid as inflammatory mediators of endotoxin shock remains uncertain. In this study the effect of LY171883, a selective leukotriene D4/E4 antagonist, on the hemodynamic alterations of endotoxin shock was assessed. Adult male rats were given an intraperitoneal injection of LY171883 (30 mg/kg) or vehicle 10 minutes prior to intravenous injection of endotoxin (15 mg/kg) or vehicle. Cardiac output, mean arterial pressure, and multiple organ blood flows were determined at 30 minutes after endotoxin or vehicle administration with 85Sr-radiolabeled microspheres. Cardiac output decreased from 32.1 +/- 2.7 ml/min/100 g in the control group to 16.3 +/- 2.7 ml/min/100 g in endotoxin-treated animals (P less than .05). Pretreatment with LY171883 blunted significantly (P less than .05) this fall in cardiac output (26.3 +/- 2.6 ml/min/100 g). Endotoxin reduced mean arterial pressure from 95 +/- 8 mm Hg in controls to 57 +/- 8 (P less than .05), which was not, however, different from control values in rats receiving the LTD4/E4 antagonist. There was also significant (P less than .05) blunting of the endotoxin-induced fall in blood flow to the heart, gastrointestinal tract, and kidneys in animals pretreated with LY171883. Our data demonstrate that this selective leukotriene D4/E4 antagonist has significant salutary actions in endotoxin shock and suggest that LTD4 and/or E4 mediate, in part, the acute hemodynamic sequelae of endotoxin shock.
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001393:Azoles / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D017999:Leukotriene E4; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000188:drug therapy; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D000098:Acetophenones; D001393:Azoles; D004731:Endotoxins; D013189:SRS-A; D013777:Tetrazoles; D017999:Leukotriene E4; C044660:LY 171883