Abstract
The beneficial role of estrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance. The use of estrogen therapy to prevent cardiovascular disease in post-menopausal women remains contentious. This study investigated the influence of aging and the menopause on the acute vasodilatory effects of estrogen using ex vivo human and murine resistance arteries. Vessels were obtained from young (2.9 ± 0.1 months) and aged (24.2 ± 0.1 and 28.9 ± 0.3 months) female mice and pre- (42.3 ± 0.5 years) and post-menopausal (61.9 ± 0.9 years) women. Aging was associated with profound structural alterations of murine uterine arteries, including the occurrence of outward hypertrophic remodeling and increased stiffness. Endothelial and smooth muscle function were diminished in uterine (and tail) arteries from aged mice and post-menopausal women. The acute vasodilatory effects of 17β-estradiol (non-specific estrogen receptor (ER) agonist), PPT (ERα-specific agonist) and DPN (ERβ-specific agonist) on resistance arteries were attenuated by aging and the menopause. However, the impairment of estrogenic relaxation was evident after the occurrence of age-related endothelial dysfunction and diminished distensibility. The data indicate, therefore, that chronological resistance arterial aging is a prominent factor leading to weakened vasodilatory action of estrogenic compounds.
Highlights
The beneficial role of estrogen in the vascular system may be due, in part, through reduction of peripheral vascular resistance
It has been proposed that estrogen activates endothelial nitric oxide synthase, endothelial prostacyclin and endothelium-derived hyperpolarizing (EDH) factor, which act on adjacent smooth muscle cells to induce relaxation[7,8,9,10,11,12,13]
The acute vasodilatory effects of estrogen have previously been established but there is little information about how these arterial responses are influenced by the menopause and advancing age
Summary
Post-menopausal deprivation of female sex hormones, primarily estrogen, may be related to the increased CVD risk in aging women[5]. Consistent with the proposed cardiovascular protective role of estrogen, early observational studies, such as the Nurses’ Health Study, suggested estrogen therapy might reduce the risk of CVD in post-menopausal women[23]. Subsequent re-analysis of the Women’s Health Initiative data revealed a trend for a lower risk of coronary heart disease in hormone-treated women from the youngest age group. This suggested the possibility of a ‘timing’ hypothesis wherein MHT initiated within 10 years of the menopause could be beneficial to CVD health[27,28,29]. Recent evidence has highlighted the role for aging per se, independent of menopausal status, in female cardiovascular risk[31,32]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
