Bursting with flexibility: responsiveness of sympathetic burst size in older women and men

There is a marked increase in the risk of hypertension as people age. Contributing mechanisms include both increased activity of sympathetic vasoconstrictor nerves and increased vascular stiffness (Narkiewicz et al. 2005; Okada et al. 2012). In younger women, resting blood pressure and the risk of hypertension are (on average) lower than in men, and resting sympathetic vasoconstrictor nerve activity tends to be lower too. Around the time of menopause, both sympathetic nerve activity and blood pressure tend to increase, and the risk of hypertension meets and sometimes exceeds that seen in men of similar age (Narkiewicz et al. 2005). Furthermore, factors that offset the pressor effects of sympathetic nerve activity in younger women (e.g. beta-adrenergic vasodilation) are minimal or absent after menopause (Hart et al. 2011). While these observations had led some investigators (including myself) to theorize that the regulation of blood pressure in women becomes ‘more like that in men’ after menopause, it turns out that the answer to that question is a definitive ‘No’. Within the complexity of factors that contribute to a given resting level of arterial blood pressure, it has become clear that there are important integrative mechanisms that are distinctly different between older men and older women. For example, post-menopausal women have been shown to have stiffer carotid and aortic arteries, thought to contribute to a decreased ability of the barosensory areas to respond to changes in pressure (Okada et al. 2012). Indeed, the same women had lower spontaneous sympathetic baroreflex sensitivity compared with men of similar age, when sensitivity was assessed using burst incidence (Okada et al. 2012). Furthermore, in groups of hypertensive older men and women, sympathetic neural and haemodynamic (pressor) responses to head up tilt were augmented in the women compared with the men (Badrov et al. 2020), a phenomenon which appeared to involve a greater number of active neurons per sympathetic burst in the women. Recently, Okada and colleagues evaluated how sex differences in sympathetic neurovascular mechanisms might contribute to differences in resting blood pressure regulation between older men and women (Okada et al. 2020). They measured peroneal muscle sympathetic nerve activity, blood pressure, cardiac output and carotid artery stiffness in groups of men and women in their late 60s and early 70s. They found that, overall, mean blood pressure and sympathetic nerve activity at rest were similar between the men and women. The amount of time between any two consecutive sympathetic bursts (what the authors called the ‘burst interval’) was on average lower in the women, and the variability in burst intervals within a given subject was also less. Burst area, on average, was not different between the two groups, but when the authors looked at the ratio between variability (range) in burst area and variability in burst interval, it turned out this ratio was significantly higher in the women. This higher ‘variation ratio’ suggests that the women had more ‘flexibility’ in their ability to change burst area relative to their ability to change burst interval while regulating blood pressure during supine rest (Okada et al. 2020). The authors’ subsequent baroreflex analysis bore this out. They showed that when sympathetic baroreflex sensitivity was calculated using sympathetic burst area (au/burst/mmHg), responsiveness of burst area to changes in blood pressure was greater in women with stiffer carotid arteries, and was less in women with less stiff arteries. This relationship did not exist in the older men. The greater responsiveness of burst area (size) seemed to offset the decreased sensitivity in the women when measured by burst incidence, such that the beat to beat variability in resting blood pressure was not different between the groups (Okada et al. 2020). As seen in the present report from Okada et al., mean blood pressure values may be similar in groups of older men and women. Nonetheless, the distinct mechanisms by which each group achieves those blood pressure levels is important in understanding why older men and women may respond differently to perturbations ranging from activities of daily living to clinical interventions. Thus, the findings of Okada and colleagues, and other studies like this which delve into the intricacies of integrative sympathetic mechanisms, have important implications for both the basic understanding and the clinical treatment of cardiovascular function across the lifespan. The views, opinions, and/or findings contained in this article are those of the authors and should not be construed as an official United States Department of the Army position, or decision, unless so designated by other official documentation. Approved for public release; distribution unlimited. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. None. Sole author. Medical Research and Materiel Command.