title: Evaluation of the role of superoxide anions in endotoxin-induced impairment of beta-adrenoceptor-mediated vasodilation in equine digital veins.
abstract: OBJECTIVE
  To investigate the role of superoxide anions in the lipopolysaccharide (LPS)-induced impairment of beta-adrenoceptor-mediated equine digital vein (EDV) vasodilation.
  
  
  METHODS
  EDVs isolated from forelimbs of 24 healthy adult horses.
  
  
  METHODS
  Endothelium-intact or endothelium-denuded EDV rings were incubated with or without LPS (10 microg/mL) of Escherichia coli (O55:B5) for 4 hours. Cumulative concentration-relaxation curves resulting from administration of isoprenaline, a nonselective beta-adrenoceptor agonist, or from administration of SR 58611A, a selective beta(3)-adrenoceptor agonist, were recorded in phenylephrine-preconstricted EDVs in the absence or the presence of superoxide dismutase (200 U/mL). Isoprenaline-induced relaxation was also evaluated with or without the cyclooxygenase inhibitors indomethacin (10 microM) and NS-398 (10 microM).
  
  
  RESULTS
  Isoprenaline and SR 58611A induced concentration-dependent relaxation of EDV rings, which was inhibited by LPS exposure. Superoxide dismutase abolished the inhibitory effect of LPS on the isoprenaline- and SR 58611A-mediated relaxation. Pretreatment of the LPS-treated EDVs with indomethacin or NS-398 restored the isoprenaline-mediated relaxation and abolished the LPS-induced impairment to a similar extent as superoxide dismutase.
  
  
  CONCLUSIONS
  Results supported a role of superoxide anions in the LPS-induced impairment of beta-adrenoceptor-mediated EDV vasodilation. The LPS-induced oxidative stress in EDVs may contribute to vascular dysfunctions associated with laminitis in horses.
authors.affiliation: ONIRIS, Unit of Animal Pathophysiology and Functional Pharmacology (UPSP 5304), Atlanpole-La C.hantrerie, BP 40706, Nantes, F-44307, France. yassine.mallem@oniris-nantes.fr
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Mallem
authors.forename: Aurélie
authors.initials: A
authors.lastname: Thuleau
authors.forename: Jacques
authors.initials: J
authors.lastname: Noireaud
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Desfontis
authors.forename: Marc
authors.initials: M
authors.lastname: Gogny
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004731:Endotoxins / Q000633:toxicity*; D005552:Forelimb / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D006736:Horses; D007545:Isoproterenol / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014034:Toes / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins / Q000187:drug effects / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D004731:Endotoxins; D011943:Receptors, Adrenergic, beta; D013764:Tetrahydronaphthalenes; D009599:Nitroprusside; D007545:Isoproterenol; D000109:Acetylcholine; C076252:amibegron