title: Endothelial dysfunction in an ovine model of collagen-induced arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) induces systemic inflammation, producing a range of co-morbidities including cardiovascular disease. An early vascular change is endothelial dysfunction, characterized by reduced endothelium-dependent vasodilation. The aim of this study was to assess endothelial function in isolated coronary and digital arteries using an ovine model of collagen-induced RA.
  
  
  METHODS
  Sheep were culled following induction of arthritis, and their endothelial function was compared to that of normal sheep. Paired arterial segments were mounted in a wire myograph and dilated with endothelium-dependent vasodilators [bradykinin, serotonin, carbachol and adenosine diphosphate (ADP); linked to either Gi or Gq signalling pathways] and endothelium-independent dilators (adenosine and sodium nitroprusside) to construct cumulative concentration-response curves.
  
  
  RESULTS
  Coronary arteries from arthritic sheep exhibited a significantly greater EC50 value for bradykinin-induced relaxation compared to non-arthritic controls (2.9 × 10(-8) M for arthritic sheep vs. 8.6 × 10(-9) M for controls). Digital arteries from arthritic sheep also exhibited a significantly greater EC50 for relaxation to ADP and a significant decrease in the carbachol maximal response. Responses to sodium nitroprusside were unchanged in both coronary and digital arteries.
  
  
  CONCLUSIONS
  Sheep with RA demonstrated attenuated arterial relaxation to endothelium-dependent vasodilators. This may provide a useful model of endothelial dysfunction in chronic inflammatory conditions. The dysfunction did not appear to be associated with one specific G-protein signalling pathway.
authors.affiliation: Faculty of Veterinary Science, The University of Melbourne, Parkville, Vic., Australia.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Dooley
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Washington
authors.forename: Anwar
authors.initials: A
authors.lastname: Abdalmula
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Tudor
authors.forename: Wayne G
authors.initials: WG
authors.lastname: Kimpton
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005121:Extremities / Q000098:blood supply*; D005260:Female; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents