Endotoxic
shock is associated with increased metabolism of
arachidonic acid to
thromboxane (Tx) and
prostaglandins. This investigation examined the effects of two structurally dissimilar inhibitors of (Tx)
synthetase on Salmonella enteritidis
endotoxin (LPS) (15 mg/kg)-induced alterations in cardiac output and organ blood flow in Long-Evans rats. An
imidazole derivative, 7(1-imidazolyl) heptanoic
acid (7-IHA), and
sodium -(E)-3-[4-(3-pyridyl-methyl)phenyl]-2-
methacrylate (OKY-1581) were injected intravenously at 30 and 5 mg/kg, respectively, 30 min before injection with
endotoxin. Cardiovascular function was assessed 30 min post-LPS with Sr-85 labeled
microspheres under light
ether anesthesia. Injection of
endotoxin caused a 60% decrease in cardiac output (34.0 +/- 2.7 ml/min/100 g
body weight in control rats) and a 38.9% decrease in systolic arterial pressure. Both Tx
synthetase inhibitors significantly (p less than 0.05) attenuated the decrease in cardiac output, although only 7-IHA improved blood pressure. Pretreatment with 7-IHA or
OKY-1581 significantly (p less than 0.05) attenuated the LPS-induced decrease in renal perfusion. Lung nutrient blood flow (1.1 +/- 0.2 ml/min/g lung) decreased nearly 70% in
shock. Both Tx
synthetase inhibitors prevented this reduction. LPS
shock resulted in approximately a 30% decrease in brain blood flow. 7-IHA significantly (p less than 0.05) improved flow, while
OKY-1581 was without apparent effect. Splanchnic blood flow was likewise improved by 7-IHA and
OKY-1581. Liver blood flow, 55% less than values of the control group in
shock (p less than 0.05), was returned to values of the controls by both inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)