title: Effect of lipopolysaccharide on the production of prostaglandin E2 and inhibition of uterine contractions by nitric oxide in pregnant inducible nitric oxide synthase knockout mice.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the effect of lipopolysaccharide (LPS) on the production of prostaglandin E2 (PGE2) and inhibition by nitric oxide (NO) of spontaneous contractions of uterine rings from pregnant inducible isoform of nitric oxide synthase knockout (iNOS KO) mice.
  
  
  METHODS
  iNOS KO and wild-type mice were sacrificed 6 h after intraperitoneal (i.p.) administration of LPS on day 14 of gestation. Uterine rings were equilibrated in Krebs-Henseleit solution for isometric tension recording. In part of the uterine rings, placental tissues were left attached. The bathing solution was analyzed for PGE2 by radioimmunoassay. Changes in spontaneous contractions in response to cumulative concentrations of L-arginine, diethylamine/nitric oxide (DEA/NO), and 8-bromo-cyclic guanosine monophosphate (8-br-cGMP) were determined.
  
  
  RESULTS
  Treatment with LPS increased PGE2 production by uterine rings from wild-type and iNOS-KO mice. DEA/NO and 8-br-cGMP inhibited spontaneous contractions in uterine rings in the absence or presence of placenta, in both LPS-treated and LPS-untreated animals. LPS treatment attenuated maximal inhibition induced by the agents, both in the absence and presence of placental tissues in iNOS KO and wild-type mice.
  
  
  CONCLUSIONS
  LPS induces PG production in mice myometrium that is not dependent on the integrity of iNOS, while LPS could induce pathophysiological iNOS obstruct uterine quiescence by physiological iNOS. Infection affects uterine contractile activity through PG production, as well as through placental and genetic factors. NO may be a double-edged sword in pregnant mice myometrium.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Fukushima Medical University, Fukushima, Japan. hide-t@fmu.ac.jp
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Okawa
authors.forename: Kimisato
authors.initials: K
authors.lastname: Asano
authors.forename: Keiya
authors.initials: K
authors.lastname: Fujimori
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone