The impact of ageing and sex on sympathetic neurocirculatory regulation

Abstract

The sympathetic nervous system represents a critical mechanism for homoeostatic blood pressure regulation in humans. This review focuses on age-related alterations in neurocirculatory regulation in men and women by highlighting human studies that examined the relationship between muscle sympathetic nerve activity (MSNA) acquired by microneurography and circulatory variables (e.g., blood pressure, vascular resistance). We frame this review with epidemiological evidence highlighting sex-specific patterns in age-related blood pressure increases in developed nations. Indeed, young women exhibit lower blood pressure than men, but women demonstrate larger blood pressure increases with age, such that by about age 60 years, blood pressure is greater in women. Sympathetic neurocirculatory mechanisms contribute to sex differences in blood pressure rises with age. Muscle sympathetic nerve activity increases with age in both sexes, but women demonstrate greater age-related increases. The circulatory adjustments imposed by MSNA - referred to as neurovascular transduction or autonomic (sympathetic) support of blood pressure - differ in men and women. For example, whereas young men demonstrate a positive relationship between resting MSNA and vascular resistance, this relationship is absent in young women due to beta-2 adrenergic vasodilation, which offsets alpha-adrenergic vasoconstriction. However, post-menopausal women demonstrate a positive relationship between MSNA and vascular resistance due to a decline in beta-2 adrenergic vasodilatory mechanisms. Emerging data suggest that greater aerobic fitness appears to modulate neurocirculatory regulation, at least in young, healthy men and women. This review also highlights recent advances in microneurographic recordings of sympathetic action potential discharge, which may nuance our understanding of age-related alterations in sympathetic neurocirculatory regulation in humans.

Keywords: Ageing; Blood pressure; Microneurography; Muscle sympathetic nerve activity; Neural control of the circulation; Neurovascular transduction; Sex differences.

Figure 1.. Trends in blood pressure with ageing in men and women.

Blood pressure rises steadily with age in healthy humans in developed nations. However, sex-specific blood pressure trajectories exist across the life course. Young women exhibit lower blood pressure than men, but the magnitude of blood pressure increase is greater in women than men. At about 60 years, men and women’s blood pressure intersects and from this point onwards, women demonstrate greater systolic blood pressure than men. Figure based on data from [3,4].

Figure 2.. Representative integrated muscle sympathetic nerve activity and sympathetic action potential discharge in a healthy individual.

The integrated neurogram highlights that muscle sympathetic nerve activity (MSNA) is fundamentally characterized by bursts of activity with time-varying frequency and size. In this figure, APs were detected and extracted from the filtered neurogram using a continuous wavelet transform [39]. The filtered neurogram and the detected action potentials (AP) show that MSNA bursting discharge is attributed to synchronous firing of varying-sized sympathetic APs. Fundamentally, larger integrated bursts are comprised by greater AP content and larger AP firing. Featured in the magnified inset at the bottom of the figure are the sympathetic AP clusters, representing APs of similar morphology, that comprise one selected MSNA burst. The size of each AP cluster is related to the sympathetic c-fibre that generated the AP. In the magnified inset, the AP clusters firing in the selected burst are organized by peak-to-peak amplitude, from smallest to largest. The number of times each AP cluster fired in this selected burst is displayed in parentheses: two AP clusters each fired once, one AP cluster fired two times, and one AP cluster fired five times, for a total of nine APs firing in the selected burst. For simplicity, not shown in this figure are asynchronously discharging sympathetic APs which fire between synchronous bursts of MSNA. The interested reader is directed to Salmanpour et al. [39] and Shoemaker et al. [25] for more information regarding the continuous wavelet transform for sympathetic AP detection and discharge sympathetic AP discharge patterns in humans.

Figure 3.. Trends in muscle sympathetic nerve activity with ageing in men and women.

In healthy normotensive individuals, muscle sympathetic nerve activity (MSNA) burst frequency approximately doubles from the age of 20 to 70 years. However, the magnitude of MSNA increase with age differs in men and women. Young women have lesser MSNA burst frequency than men. Both sexes exhibit increases in MSNA with age but the magnitude of change is greater in women than men. Figure based on data from [53,73].