Bursting our understanding of baroreflex control in older adults: Sex differences in the neurovascular mechanisms regulating blood pressure

The arterial baroreflex is a vital homeostatic mechanism involved in regulating blood pressure (BP). When disequilibrium is detected, stretch-sensitive baroreceptors provide afferent feedback to stabilise BP through modulating heart rate and muscle sympathetic nervous activity (MSNA). The magnitude of the sympathetic response to changes in BP is termed the BP buffering capacity and is measured as baroreflex sensitivity (BRS). With age, this buffering capacity deteriorates, and risks of hypertension and cardiovascular disease concomitantly increase. Nevertheless, this age-related deterioration is complex and multifactorial. Subpopulations of baroreceptor afferents range in sensitivity and display divergent excitation thresholds to different BP stimuli. Therefore, baroreflex-mediated sympathetic responses are thought to be independently modulated and vary with age. Furthermore, distinct sex differences appear to exist in the neurovascular mechanisms that regulate BP in older adults. Okada et al. (2011) reported increased arterial stiffness and lower BRS, using burst occurrence, in older women compared with older men. This increased arterial stiffness was inversely correlated with BRS across both sexes, suggesting that with age increased arterial stiffness impairs the pressure-sensing ability of the baroreceptors. Nonetheless, integrated sympathetic BRS has been described as comparable between older men and women (Studinger et al. 2009). This discrepancy may be explained by the difference in the mean age of participants in these two studies. However, this finding also hints at the possibility of compensatory neural modules which recoup the impaired response of MSNA burst occurrence in women. Two neural modules have been suggested to regulate the occurrence and area of MSNA bursts separately (Kienbaum et al. 2001). Therefore, it is possible that when burst occurrence regulation is impaired, burst area regulation becomes the dominant BP buffering system. However, until recently, research into these compensatory mechanisms has been lacking. In a recent issue of the Journal of Physiology, Okada et al. (2020) investigated sex differences in the mechanisms regulating resting BP in older adults. In 61 healthy males and females (68 ± 7 years), peroneal MSNA was assessed via microneurography during supine rest. The distributions of MSNA burst area and intervals were evaluated and BRS was analysed using burst occurrence and area simultaneously. These values were then compared with changes in arterial stiffness and BP. Carotid β-stiffness was derived using B-mode ultrasonography, whilst BP was assessed using finger photoplethysmography and electrosphygmomanometry. Additionally, heart rate and cardiac output were measured using electrocardiography and the modified acetylene rebreathing technique. The researchers hypothesised that the ratio of variation in MSNA burst area to burst occurrence would be greater in older women than in older men. They also postulated that increased arterial stiffness would correlate with BRS calculated using burst area in an opposite direction to BRS calculated using burst occurrence. Overall, Okada et al. (2020) found that BP variability was similar among older men and women. However, the mechanisms regulating this variability were different. Women demonstrated increased arterial stiffness compared with men and a lower range of MSNA burst intervals. The distribution of burst area was comparable across the sexes, but the ratio in variation of burst area to burst occurrence was larger in women. These results suggested that MSNA burst occurrence in women was impaired and that it was compensated for by increased regulation of burst area. These findings were subsequently confirmed by an analysis of BRS. When assessed using burst occurrence, BRS overall was lower in women but it decreased equally with arterial stiffness in both sexes. Meanwhile, BRS assessed using burst area was only lower in women after adjusting for arterial stiffness, and it increased in women but not in men as arterial stiffness increased. These results indicate that MSNA burst size becomes more adaptable to changes in BP in women to compensate for the impaired regulation of burst occurrence. This compensatory mechanism is adequate enough that BP is regulated to the same extent in older women as it is in older men. Okada et al. (2020) present a well-executed study with robust methodologies, enabling the sex differences in the baroreflex control of BP in older adults to be explored. The study was the first to compare BRS using burst occurrence and area simultaneously. Therefore, it contributes novel findings which advance the current field of arterial baroreflex research. The results support the concept of two distinct neural mechanisms underpinning the regulation of MSNA burst occurrence and burst area separately, thus highlighting the importance of evaluating both in clinical and research settings. Additionally, the findings help resolve discrepancies in previous literature where BRS was assessed using either burst occurrence or burst area separately (Studinger et al. 2009; Okada et al. 2011). Nevertheless, pioneering work like this often raises a plethora of questions and challenges, and these novel findings merit further discussion with regard to: sex differences in the prevalence of hypertension, the mechanisms responsible for detecting impaired burst occurrence, age differences in burst area regulation and the clinical implications. Although some useful insights into the sex differences in BP regulation in older adults can be gained from this study, a conundrum that pertains is why hypertension is more prevalent in elderly women than elderly men. Okada and colleagues demonstrated that there are compensatory neural mechanisms which allow older women to regulate BP to the same extent as men. Yet, large epidemiological studies show that hypertension is more prevalent