Neurovascular control of blood pressure is influenced by aging, sex, and sex hormones

Abstract

In this review, we highlight that the relationship between muscle sympathetic nerve activity (MSNA) and mean arterial pressure is complex, differs by sex, and changes with age. In young men there is an inverse relationship between MSNA and cardiac output where high MSNA is compensated for by low cardiac output. This inverse relationship is not seen in older men. In young women sympathetic vasoconstriction is offset by β-adrenoreceptor mediated vasodilation, limiting the ability of young women to maintain blood pressure in response to orthostatic stress. However, β-mediated dilation in women is attenuated with age, leading to unopposed α-adrenergic vasoconstriction and a rise in the direct transduction of MSNA into increases in blood pressure. We propose that these changes with age and menopausal status are major contributing factors in the increased prevalence of hypertension in older women. In addition to aging, we highlight that changes in sex hormones in young women (across the menstrual cycle, with oral contraceptive use, or with pregnancy) influence MSNA and the transduction of MSNA into increases in blood pressure. It is likely that the β-adrenergic receptors and/or changes in baroreflex sensitivity play a large role in these sex differences and changes with alterations in sex hormones.

Keywords: autonomic function; blood pressure; neural control of blood pressure; sex differences.

Fig. 1.

Mechanisms that contribute to the age-related increase in blood pressure in women. Sympathetic vasoconstriction is largely offset by β-adrenoreceptor-mediated vasodilation in young women. With age, β-mediated dilation is reduced, which leads to unopposed α-adrenergic restriction and augments the transduction of SNA into increases in blood pressure. Age-related alterations in β-mediated dilation, α-adrenergic constriction, and vascular transduction are major factors that likely contribute to the increased prevalence of hypertension in women, particularly after the onset of menopause. Estrogen and normal sex-specific conditions, such as the menstrual cycle, pregnancy, and menopause, play an important role in these relationships that is still being elucidated. Age-related changes in nitric oxide and prostaglandin-mediated vasodilation could further raise blood pressure. Additionally, reduction in vasodilator prostaglandins could increase the release of norepinephrine. SNA, sympathetic nervous system activity; α, α-adrenergic receptor; β, β-adrenergic receptor; RAAS, renin-angiotensin-aldosterone system; NO, nitric oxide; PGE₂, prostaglandin E; PGI₂, prostaglandin I₂.