This study investigated the effect of a novel
LTD4 receptor antagonist
LY203647 on Salmonella enteritidis
endotoxin-induced
shock sequelae in anesthetized rats.
LY203647 (30 mg/kg i.v.) or vehicle was given 10 min prior to
endotoxin (10 mg/kg i.v.) or its vehicle, and the hematocrit, mean arterial pressure and circulating leukocyte counts were determined.
LY203647 significantly inhibited
endotoxin-induced hemoconcentration up to 90 min post-
endotoxin (46.7 +/- 1.3 vs. 51.9 +/- 2.4% at 30 min post-
endotoxin, 45.9 +/- 1.1 vs. 53.1 +/- 1.4% at 90 min post-
endotoxin, N = 8-9, P less than 0.05). The
endotoxin-induced decreases in mean arterial pressure were also attenuated by
LY203647, -29 +/- 5 vs. -56 +/- 9 mm Hg at 60 min post-
endotoxin and -42 +/- 4 vs. -60 +/- 9 mm Hg at 90 min post-
endotoxin (N = 9-10, P less than 0.05).
LY203647 also attenuated
endotoxin-induced decreases in leukocyte count in arterial blood. A study of differential counts in circulating leukocytes (N = 3) showed that
endotoxin induced complete disappearance in circulating neutrophils. The circulating lymphocyte count was decreased by 30 +/- 10 and 41 +/- 1% at 15 and 30 min post-
endotoxin, respectively.
LY203647 inhibited
endotoxin-induced
lymphopenia (P less than 0.05) but failed to alter
endotoxin-induced
neutropenia. These data suggest that
LTD4 may play an important role in mediating hemoconcentration, hypotensive and lymphocytopenic sequelae of
endotoxin shock.