title: Aortic function is compromised in a rat model of polycystic ovary syndrome.
abstract: BACKGROUND
  Arterial mechanical parameters are modified in women with polycystic ovary syndrome (PCOS), before and during pregnancy. This study tested the hypothesis that aortic mechanics and endothelial function are modified in the mifepristone-treated rat model of PCOS.
  
  
  METHODS
  Female rats injected daily with mifepristone or vehicle for 7-9 days were assessed by ultrasound to allow estimation of aortic stiffness index and compliance. The influence of acetylcholine (ACh) and sodium nitroprusside (SNP) on dissected phenylephrine-contracted aortic rings was assessed.
  
  
  RESULTS
  Aortic compliance was reduced by 67% in mifepristone-treated rats versus controls (P<0.05), while stiffness index was increased 2.3-fold (P<0.02). ACh-induced dilation was less in aortic rings from mifepristone-treated rats (P=0.022) and was less sensitive to the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (P<0.001), while SNP-induced dilation was greater (P=0.001).
  
  
  CONCLUSIONS
  Aortic mechanics in vivo and endothelial function in vitro were consistently perturbed in mifepristone-treated rats. Aortic ring behaviour suggested that NO release was depressed or degradation elevated, with a compensatory increase in NO sensitivity and/or activation of a non-NO-mediated relaxation mechanism. The mifepristone-treated rat is a valid model for investigation of the vascular deficits seen in PCOS.
authors.affiliation: Ultrasound Department, North Middlesex Hospital, and Department of Surgery, Royal Free and University College Medical School, University College London, UK.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Lakhani
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Yang
authors.forename: Audrey
authors.initials: A
authors.lastname: Dooley
authors.forename: Essam
authors.initials: E
authors.lastname: El-Mahdi
authors.forename: Maryse
authors.initials: M
authors.lastname: Sundaresan
authors.forename: Susan
authors.initials: S
authors.lastname: McLellan
authors.forename: Richard
authors.initials: R
authors.lastname: Bruckdorfer
authors.forename: Andrew
authors.initials: A
authors.lastname: Leonard
authors.forename: Alexander
authors.initials: A
authors.lastname: Seifalian
authors.forename: Paul
authors.initials: P
authors.lastname: Hardiman
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007986:Luteinizing Hormone / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007328:Insulin; D009599:Nitroprusside; D010656:Phenylephrine; D015735:Mifepristone; D007986:Luteinizing Hormone; D000109:Acetylcholine