This study examined 1) the effects of infusion of
LTB4 and 2) the potential role of
LTB4 in the sequelae to endotoxic
shock in the rat. Control rats were anesthetized with
Ketamine/
xylazine and given
LTB4 (2 micrograms/kg) bolus i.v. followed by a 1 microgram/kg/min infusion for 10 min.
LTB4 induced systemic
hypotension and a three-fold increase in circulating band neutrophils which contributed to a 70% increase (P less than 0.05) in the total peripheral neutrophil count.
LTB4 did not cause changes in circulating mature (segmented) neutrophils, lymphocytes, platelets, or hematocrits. Pretreatment (1 min) with LY233978, an
LTB4 antagonist (10 mg/kg bolus i.v.), inhibited
LTB4-induced systemic
hypotension (-16.1 +/- 6.1 mmHg [n = 3] vs. -38.8 +/- 5.9 mmHg [n = 4], P less than 0.05). Salmonella enteritidis
endotoxin (10 mg/kg bolus i.v.) induced systemic
hypotension, hemoconcentration,
leukopenia, and
thrombocytopenia, which was greatest at 5 and 15 min postendotoxin. The
leukopenia was characterized by
lymphopenia, band
neutropenia, and segmented
neutropenia. LY233978 (10 mg/kg bolus i.v. immediately before
endotoxin administration and followed by an infusion at 0.67 mg/kg/min for 90 min) attenuated
endotoxin-induced hemoconcentration at 60 and 90 min postendotoxin (P less than 0.05), and systemic
hypotension at 15 min postendotoxin (P less than 0.05). The
LTB4-receptor antagonist
LY255283 (10 mg/kg bolus i.v., 10 min before
endotoxin followed by a 5 mg/kg bolus i.v. 30 min postendotoxin) completely inhibited
endotoxin-induced systemic
hypotension and partially attenuated
endotoxin-induced hemoconcentration from 15 min to 90 min postendotoxin (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)