Modulation of blood pressure by estrogen: A modeling analysis

Hypertension is a global health challenge: it affects one billion people worldwide and is estimated to account for >60% of all cases or types of cardiovascular disease. Premenopausal women have lower blood pressure and hypertension prevalence compared to age-matched men, but that female protection is lost after menopause, the onset of which marks the beginning of a rapid decline in estrogen levels. The precise mechanisms by which estrogen protects premenopausal women from hypertension have yet to be elucidated. What is known is that estrogen has a plethora of interactions with other hormone systems as well as physiological processes known or hypothesized to impact the regulation of blood pressure. Thus, an objective of this study is to identify the primary contributors to the estrogen-mediated cardiovascular protection. To accomplish that goal, we develop a blood pressure regulation model that incorporates the effects of estrogen on the renin-angiotensin system, the reactivity of renal sympathetic nervous activity, vascular tone, and renal epithelial transport. Model simulations suggest that estrogen's vasodilatory effect, especially on the afferent arterioles, is the largest cause of premenopausal women's lower blood pressure and resistance to developing hypertension. Furthermore, the model predicts that angiotensin receptor blockers are more effective than angiotensin converting enzyme inhibitors in treating hypertensive women throughout their lifespan, even as estrogen levels decline.