title: Effect of cytochrome P-450 epoxygenase and hydroxylase metabolites on rat myometrium contractility in non-pregnancy, late pregnancy and late pregnancy under inflammatory conditions.
abstract: OBJECTIVE
  The aim of the present experimental study was to assess the tocolytic effect of eicosanoids on myometrium from non-pregnant and pregnant rats with or without an induced inflammatory condition.
  
  
  METHODS
  Three hundred myometrial rings were obtained by median laparotomy from 50 Sprague-Dawley rats divided into three groups: (i) non-pregnant (n = 15); (ii) pregnant in absence (n = 20); or (iii) pregnant in presence (n = 15) of lipopolysaccharide treatment, timed at 22 days of pregnancy. Spontaneous contractile activities were compared by isometric tension measurements. The effects of epoxy- and hydroxyeicosanoids derived from arachidonic acid as well as specific enzyme inhibitors were assessed. Changes were expressed as percentage of basal activity by calculating the area under the curve as a function of drug concentration and compared to the effect of the vehicle.
  
  
  RESULTS
  A decrease in contractile activity ranging 10-25% was observed upon addition of epoxy- and hydroxyeicosanoids. Increasing epoxyeicosanoid bioavailability by inhibiting their degradation induced a tocolytic effect in the non-pregnant group (20%) and in inflammation-induced condition (40%). There was a significant difference in reactivity between groups and pregnancy condition. Semiquantification of metabolic enzymes that produce (cytochrome P-450 epoxygenase) and degrade (soluble epoxide hydrolase) epoxyeicosanoids by western blot analysis revealed that these enzymes were mainly detected in the non-pregnant group.
  
  
  CONCLUSIONS
  Eicosanoids can modify myometrial reactivity and their presence and effects are amplified in non-pregnant and in inflammation-induced condition. Our data suggest that in contrast to prostaglandins, epoxyeicosatrienoic acids are likely involved in the quiescence phase of parturition because they reduce the rhythmic contractile activity of uterine tissues in pregnant rats.
authors: Obstetrics and Gynecology, CRC E-Lebel - CHUS, Sherbrooke, Quebec, Canada; Physiology and Biophysics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors: Stéphanie
authors: S
authors: Corriveau
authors: Maryse
authors: M
authors: Berthiaume
authors: Isabelle
authors: I
authors: Girard
authors: Marc-Antoine
authors: MA
authors: Nolin
authors: Eric
authors: E
authors: Rousseau
authors: Jean-Charles
authors: JC
authors: Pasquier
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000090762:Cytochrome P-450 CYP2J2; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008954:Models, Biological; D009215:Myometrium / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D011255:Pregnancy Maintenance; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects; D014591:Uterine Diseases / Q000201:enzymology / Q000276:immunology / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid
keywords: 20-hydroxyeicosatetraenoic acid; epoxyeicosatrienoic acid; tocolytic; uterine contractile activity