Effect of lipopolysaccharide on uterine contractions and prostaglandin production in pregnant rats

OBJECTIVE: Our aim was to evaluate the effect of lipopolysaccharide on pros taglandin production and on contraction of isolated myometrial strips from preterm pregnant rats. STUDY DESIGN: Pregnant Wistar rats on day 17 of gestation were kilted 3 hou rs after intraperitoneal injection of lipopolysaccharide (1.5 mg/kg) or veh icle, with or without pretreatment with indomethacin (5 mg/kg administered intraperitoneally) 1 hour beforehand. Concentrations of endotoxin in matern al serum and amniotic fluid, prostaglandin F-2 alpha and prostaglandin E-2 in amniotic fluid, and progesterone in maternal serum were determined. Long itudinal uterine strips were prepared, placed in organ chambers with Krebs- Ringer solution, aerated with 95% oxygen and 5% carbon dioxide (37 degreesC , pH similar to7.4), and equilibrated at 1g passive tension. Concentration- contraction relationships to oxytocin were determined. Samples of bathing s olution were collected 10 minutes after the concentration of oxytocin was m axima[. Prostaglandins and progesterone were measured by radioimmunoassay a nd endotoxin was measured by the Endospecy (Seikagaku Kogyo, Tokyo, Japan) kit. RESULTS: Lipopolysaccharide treatment significantly increased the levels of prostaglandin F-2 alpha and prostaglandin E-2 in amniotic fluid. Treatment with lipopolysaccharide inhibited the production and release of proslaglan din F-2 alpha! and prostaglandin E-2 that were activated by oxytocin in ute rine strips and increased the sensitivity of strips to the contractile effe ct of oxytocin. Indomethacin did not affect the basal or the lipopolysaccha ride-activated levels of endotoxin in serum and amniotic fluid and exerted a counteraction on lipopolysaccharide-induced increases in concentrations o f prostaglandin F-2 alpha and prostaglandin E-2 in amniotic fluid. Indometh acin counteracted oxytocin-activated production and release of prostaglandi n F-2 alpha and prostaglandin Ep in uterine tissues after lipopolysaccharid e administration without changing the sensitivity of uterine strips to oxyt ocin. Concentrations of progesterone were not changed after lipopolysacchar ide, indomethacin, or their combined application, which suggests that the c hanges described were not associated with alterations in the levels of the hormone. CONCLUSIONS: The activation of the uterine contractile system by prostaglan din and oxytocin during intraamniotic infection may be one of the causes of preterm delivery A combination of an oxytocin receptor antagonist and an i nhibitor of cyclooxygenase may be beneficial in prevention or treatment of preterm labor.