Aortic function is compromised in a rat model of polycystic ovary syndrome.
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.
Lakhani
Kalpana
K
Ultrasound Department, North Middlesex Hospital, and Department of Surgery, Royal Free and University College Medical School, University College London, UK.
Yang
Wenxuan
W
Dooley
Audrey
A
El-Mahdi
Essam
E
Sundaresan
Maryse
M
McLellan
Susan
S
Bruckdorfer
Richard
R
Leonard
Andrew
A
Seifalian
Alexander
A
Hardiman
Paul
P
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
D007328:Insulin; D009599:Nitroprusside; D010656:Phenylephrine; D015735:Mifepristone; D007986:Luteinizing Hormone; D000109:Acetylcholine