Abstract 15199: Effects of Ageing on Nitric Oxide Signalling in Women: Comparison with Polycystic Ovarian Syndrome
Ageing per se represents an independent risk factor for ischemic heart disease, but the mechanism(s) underlying this effect remains controversial. Polycystic ovarian syndrome (PCOS) appears to engender premature development of heart disease, irrespective of comorbidities. We have now evaluated the impact of ageing and menopause on vascular and platelet nitric oxide (NO) signalling in normal women aged 18 to 60 years, and compared these changes with an age-matched group of PCOS subjects.
Methods: We evaluated platelet responsiveness to NO via whole blood aggregometry, vascular endothelial function and NO responsiveness using applanation tonometry, and utilized asymmetric dimethylarginine (ADMA) concentrations as an index of endogenous inhibition of NO generation.
Results: In normal women (n=132), platelet NO responsiveness (ANOVA F=9.9, p<0.0001) and vascular endothelial function (F=7.7, p<0.0001) decreased whilst ADMA increased significantly (F=6.4, p=0.0005) with age. Detailed evaluation of 40 perimenopausal women revealed no correlation between plasma oestradiol levels and changes in NO response. In PCOS subjects (n=109; Figure B) there was no significant fluctuation of NO response (F=1.9, p=0.1), vascular endothelial function (F=0.6, p=0.6) or ADMA (F=1.6, p=0.2) with age. However, NO response and vascular endothelial function were impaired (2 way ANOVA F=4.2, p=0.04 and F=5.6, p=0.02 respectively) and ADMA was elevated (F=47.0, p<0.0001) relative to normal women. Vascular NO responsiveness showed identical differences for both age and PCOS.
Conclusions: (1) Normal female ageing is associated with progressive impairment of platelet/vascular NO signalling, (2) In PCOS subjects, similar changes are already present in young adults.
- © 2012 by American Heart Association, Inc.