title: Effect of lipopolysaccharide on uterine contractions and prostaglandin production in pregnant rats.
abstract: OBJECTIVE
  Our aim was to evaluate the effect of lipopolysaccharide on prostaglandin production and on contraction of isolated myometrial strips from preterm pregnant rats.
  
  
  METHODS
  Pregnant Wistar rats on day 17 of gestation were killed 3 hours after intraperitoneal injection of lipopolysaccharide (1.5 mg/kg) or vehicle, with or without pretreatment with indomethacin (5 mg/kg administered intraperitoneally) 1 hour beforehand. Concentrations of endotoxin in maternal serum and amniotic fluid, prostaglandin F2alpha and prostaglandin E2 in amniotic fluid, and progesterone in maternal serum were determined. Longitudinal uterine strips were prepared, placed in organ chambers with Krebs-Ringer solution, aerated with 95% oxygen and 5% carbon dioxide (37 degrees C, pH approximately 7.4), and equilibrated at 1g passive tension. Concentration-contraction relationships to oxytocin were determined. Samples of bathing solution were collected 10 minutes after the concentration of oxytocin was maximal. Prostaglandins and progesterone were measured by radioimmunoassay and endotoxin was measured by the Endospecy (Seikagaku Kogyo, Tokyo, Japan) kit.
  
  
  RESULTS
  Lipopolysaccharide treatment significantly increased the levels of prostaglandin F2alpha and prostaglandin E2 in amniotic fluid. Treatment with lipopolysaccharide inhibited the production and release of prostaglandin F2alpha and prostaglandin E2 that were activated by oxytocin in uterine strips and increased the sensitivity of strips to the contractile effect of oxytocin. Indomethacin did not affect the basal or the lipopolysaccharide-activated levels of endotoxin in serum and amniotic fluid and exerted a counteraction on lipopolysaccharide-induced increases in concentrations of prostaglandin F2alpha and prostaglandin E2 in amniotic fluid. Indomethacin counteracted oxytocin-activated production and release of prostaglandin F2alpha and prostaglandin E2 in uterine tissues after lipopolysaccharide administration without changing the sensitivity of uterine strips to oxytocin. Concentrations of progesterone were not changed after lipopolysaccharide, indomethacin, or their combined application, which suggests that the changes described were not associated with alterations in the levels of the hormone.
  
  
  CONCLUSIONS
  The activation of the uterine contractile system by prostaglandin and oxytocin during intra-amniotic infection may be one of the causes of preterm delivery. A combination of an oxytocin receptor antagonist and an inhibitor of cyclooxygenase may be beneficial in prevention or treatment of preterm labor.
authors.affiliation: Department of Obstetrics and Gynecology, Fukushima Medical University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okawa
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Yaanagida
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Vedernikov
authors.forename: G
authors.initials: G
authors.lastname: Saade
authors.forename: R
authors.initials: R
authors.lastname: Garfield
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D015237:Dinoprost / Q000032:analysis / Q000096:biosynthesis; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis; D004731:Endotoxins / Q000032:analysis / Q000097:blood; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D011453:Prostaglandins; D011374:Progesterone; D010121:Oxytocin; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin