Influence of Age and Estradiol on Sympathetic Nerve Activity Responses to Exercise in Women

Abstract

Introduction: Postmenopausal women (PMW) display exaggerated increases in blood pressure (BP) during exercise, yet the mechanism(s) involved remain unclear. Moreover, research on the impact of menopausal changes in estradiol on cardiovascular control during exercise are limited. Herein, we tested the hypothesis that sympathetic responses during exercise are augmented in PMWcompared with young women (YW), and estradiol administration attenuates these responses. Methods: Muscle sympathetic nerve activity (MSNA) and mean arterial pressure (MAP) were measured in 13 PMW (58 ± 1 yr) and 17 YW (22 ± 1 yr) during 2 min of isometric handgrip. Separately, MSNA and BP responses were measured during isometric handgrip in six PMW (53 ± 1 yr) before and after 1 month of transdermal estradiol (100 μg•d −1 ). A period of postexercise ischemia (PEI) to isolate muscle metaboreflex activation followed all handgrip bouts. Results: Resting MAP was similar between PMW and YW, whereas MSNA was greater in PMW (23 ± 3 vs 8 ± 1 bursts per minute; P < 0.05). During handgrip, the increases in MSNA (PMW Δ16 ± 2 vs YW Δ6 ± 1 bursts per minute; P < 0.05) and MAP (PMW Δ18 ± 2 vs YW Δ12 ± 2 mm Hg; P < 0.05) were greater in PMW and remained augmented during PEI. Estradiol administration decreased resting MAP but not MSNA in PMW. Moreover, MSNA (PMW (−E2) Δ27 ± 8 bursts per minute versus PMW (+E2) Δ12 ± 5 bursts per minute; P < 0.05) and MAP (Δ31 ± 8 mm Hg vs Δ20 ± 6 mm Hg; P < 0.05) responses during handgrip were attenuated in PMW after estradiol administration. Likewise, MAP responses during PEI were lower after estradiol. Conclusions: These data suggest that PMW exhibit an exaggerated MSNA and BP response to isometric exercise, due in part to heightened metaboreflex activation. Furthermore, estradiol administration attenuated BP and MSNA responses to exercise in PMW.

Sympathetic vasomotor outflow during low‐intensity leg cycling in healthy older males

“…It has been suggested that the absolute (rather than the percentage) ΔMSNA exerts the most influence on target organ responses, and is therefore the most physiologically significant measure (Tanaka et al, 1999). All recent studies (Badrov et al, 2016;Gagnon et al, 2015;Lee et al, 2021;Miller et al, 2019;Notarius et al, 2019;Wenner et al, 2022), with the exception of Keller-Ross et al (2020), that compared MSNA responses to acute physiological stressors (i.e., handgrip exercise and cold pressings) between younger and older individuals reported absolute MSNA changes only. MSNA BF is related to the plasma noradrenaline concentration (Morlin et al, 1983;Ng et al, 1993;Wallin et al, 1987) and renal noradrenaline spillover (Wallin et al, 1996).…”

“…Only males were included in the present study. Several age‐related alterations may preferentially increase the likelihood of an exaggerated ABP response to exercise in females compared with males (Trinity et al., 2018; Wenner et al., 2022). Older females exhibit impaired vasodilatory capacity during exercise (Parker et al., 2008, 2010), and changes in MSNA (Matsukawa et al., 1998) and vascular dysfunction (Celermajer et al., 1994) are accelerated in postmenopausal females compared with age‐matched males.…”

The interactive effects of age and sex on the neuro‐cardiovascular responses during fatiguing rhythmic handgrip exercise

“…Specifically, in primarily male samples, either no impact of age (Greaney et al., 2013) or attenuated (Houssiere et al., 2006; Markel et al., 2003; Ng et al., 1994) sympathetic and pressor responses to exercise and PECO are reported in older adults. Conversely, post‐menopausal females demonstrate exaggerated increases in MSNA and BP during isometric exercise and PECO compared with young, pre‐menopausal females, likely due to the loss of oestradiol following menopause (Wenner et al., 2022). Taken together, these data suggest that there may be a sex‐specific impact of age on the sympathetic neurocirculatory responses to exercise and PECO.…”

Combined Citrulline and Glutathione Supplementation Improves Endothelial Function and Blood Pressure Reactivity in Postmenopausal Women

“…Impaired FMD and increased sympathetic activity are associated with the increased risk of incident hypertension in healthy postmenopausal women [ 13 , 14 ]. Our participants had a normal or elevated SBP at rest.…”

“…Endothelial dysfunction precedes the development of arterial stiffness [ 12 ] and hypertension in healthy postmenopausal women [ 13 ]. Another mechanism for hypertension in postmenopausal women is elevated sympathetic activity [ 14 ]. Systolic hypertension and consequent heart failure with preserved ejection fraction are highly prevalent in older women due to increased aortic stiffness [ 15 ] and sympathetic-mediated vasoconstriction [ 16 , 17 ].…”