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.
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.