Estrogenic vascular effects are diminished by chronological aging.

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Vascular Biology

Background:

• Estrogen's beneficial vascular effects, including reduced peripheral resistance, are known but its role in post-menopausal cardiovascular disease prevention is debated.
• Aging and menopause significantly alter vascular structure and function, potentially impacting estrogen's vasodilatory capacity.

Purpose of the Study:

• To investigate how aging and menopause affect the acute vasodilatory responses to estrogen in human and murine resistance arteries.
• To determine if age-related vascular changes precede or follow the attenuation of estrogen's vasodilatory effects.

Main Methods:

• Ex vivo analysis of uterine and tail resistance arteries from young and aged female mice, and pre- and post-menopausal women.
• Assessment of structural alterations, stiffness, and endothelial/smooth muscle function.
• Evaluation of vasodilatory responses to 17β-estradiol, ERα-specific agonist (PPT), and ERβ-specific agonist (DPN).

Main Results:

• Aging induced hypertrophic remodeling and increased stiffness in murine uterine arteries.
• Endothelial and smooth muscle function were impaired in aged mice and post-menopausal women.
• Estrogenic vasodilation (via non-specific, ERα, and ERβ agonists) was attenuated by aging and menopause, occurring after endothelial dysfunction and reduced distensibility.

Conclusions:

• Chronological aging of resistance arteries is a primary factor diminishing the vasodilatory action of estrogenic compounds.
• Age-related vascular changes, including endothelial dysfunction, contribute to the reduced effectiveness of estrogen in promoting vasodilation.