Effect of the LTD4 receptor antagonist LY203647 on endotoxic shock sequelae in the rat.
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.
Li
E J
EJ
Department of Physiology, Medical University of South Carolina, Charleston 29425.
Cook
J A
JA
Ashton
S
S
Wise
W C
WC
Halushka
P V
PV
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004731:Endotoxins / Q000633:toxicity*; D006400:Hematocrit; D007958:Leukocyte Count / Q000187:drug effects*; D007970:Leukopenia / Q000209:etiology; D008231:Lymphopenia / Q000209:etiology; D008297:Male; D009503:Neutropenia / Q000209:etiology; D051381:Rats; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology*
D000098:Acetophenones; D004731:Endotoxins; D013189:SRS-A; D013777:Tetrazoles; C061324:LY 203647