Sex Hormones and Sympathetic Nerve Activity

The purpose of this thesis was to test the hypothesis that changes in circulating sex hormone levels are associated with changes in muscle sympathetic nerve activity. The hypothesis was tested through the comparison of low- (early follicular [EF]) and high-hormone (midluteal [ML]) phases of the menstrual cycle and of hormonal contraceptive use (low hormone [LH] versus high hormone [HH]). The microneurography technique was used to compare both the frequency and size of bursts in muscle sympathetic nerve activity (MSNA) at baseline and during two sympatho-excitatory maneuvers: baroreceptor unloading elicited through lower body negative pressure, and chemoreflex stimulation elicited through a hypoxic-hypercapnic end-inspiratory apnea. Sympathetic responses to chemoreflex stimulation were also compared between women and men. All associations between MSNA and hormone phases occurred similarly between users and non-users of hormonal contraceptives. At baseline, MSNA was relatively elevated during the high hormone phases (ML and HH), at which point baseline sympathetic activity was similar to that observed in men. However, stimulation of the chemoreflex resulted in greater sympathetic activation during the low hormone phases (EF and LH) relative to the high hormone phases. Further, this hormone phase effect was mediated largely by greater increases in burst size, rather than the burst frequency component. This may indicate that central integration sites for MSNA are affected by circulating sex hormone levels. Finally, the sympathetic responses to baroreceptor unloading were graded to reductions in stroke volume, which, in turn, were affected by hormone levels. However, no evidence was observed to suggest a change in the central integration of baroreceptor afferent input occurred across phases of the menstrual cycle or hormonal contraceptive use in terms of baroreflex function. Together, these studies confirm that sympathetic nerve activity at baseline and sympathetic recruitment during chemoreflex stimulation are affected by hormone phase, while baroreceptor-mediated responses are not affected by the transition from low (EF and LH) to high hormone phases (ML and HH)

Sympathetic neural recruitment strategies: Responses to severe chemoreflex and baroreflex stress

© 2015 the American Physiological Society. This study tested the hypothesis that neural coding patterns exist within the autonomic nervous system. We investigated sympathetic axonal recruitment strategies in humans during chemoreflex- and baroreflexmediated sympathoexcitation using a novel action potential (AP) analysis technique. Muscle sympathetic nerve activity (microneurography) was collected in 11 young individuals (6 females) during baseline and two subsequent protocols: 1) severe chemoreflex stimulation (maximal end-inspiratory apnea following rebreathe), and 2) severe baroreceptor unloading (-80 mmHg lower body negative pressure; LBNP). When compared with each respective baseline, apnea and LBNP increased AP frequency and mean AP content per sympathetic burst (all P \u3c 0.01). When APs were binned according to peak-to-peak amplitude (i.e., into “clusters”), total clusters detected increased during both apnea (Δ7 ± 5; P = 0.0009) and LBNP (Δ11 ± 8; P = 0.0012) compared with baseline. This was concomitant to an increased number of active clusters per burst during apnea (Δ3 ± 1; P = 0.0001) and LBNP (Δ3 ± 3; P = 0.0076). At baseline and during apnea (R2 = 0.98; P = 0.0001) and LBNP (R2 = 0.95; P = 0.0001), a pattern emerged whereby AP cluster latency decreased as cluster size increased. Furthermore, the AP cluster latency profile was shifted downward during apnea (~53 ms) and upward during LBNP (~31 ms). The data indicate that variations in synaptic delays and latent subpopulations of larger axons exist as recruitment strategies for sympathetic outflow. The synaptic delay component appears to express reflex specificity, whereas latent subpopulation recruitment demonstrates sensitivity to stress severity

Effects of one\u27s sex and sex hormones on sympathetic responses to chemoreflex activation

© 2016 The Physiological Society. Sex-dependent differences in baseline sympathetic nerve activity are established, but little information exists on the influence of sex on sympathetic activation during chemoreflex stimulation. In this article, we review the evidence for the effect of sex on chemoreflex-driven increases in sympathetic nerve activity. We also review recent studies which indicate that changes in circulating sex hormones, as initiated by the menstrual cycle and hormonal contraceptive use, elicit notable changes in the muscle sympathetic activation during chemoreflex stimulation

Heterogeneous baroreflex control of sympathetic action potential subpopulations in humans

© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society Key points: Emission patterns in muscle sympathetic nerve activity stem from differently sized action potential (AP) subpopulations that express varying discharge probabilities. The mechanisms governing these firing behaviours are unclear. This study investigated the hypothesis that the arterial baroreflex exerts varying control over the different AP subpopulations. During baseline, medium APs expressed the greatest baroreflex slopes, while small and large APs exhibited weaker slopes. On going from baseline to lower body negative pressure (LBNP; simulated orthostatic stress), baroreflex slopes for some clusters of medium APs expressed the greatest increase, while slopes for large APs also increased but to a lesser degree. A subpopulation of previously silent larger APs was recruited with LBNP but these APs expressed weak baroreflex slopes. The arterial baroreflex heterogeneously regulates sympathetic AP subpopulations, exerting its strongest effect over medium APs. Weak baroreflex mechanisms govern the recruitment of latent larger AP subpopulations during orthostatic stress. Abstract: Muscle sympathetic nerve activity (MSNA) occurs primarily in bursts of action potentials (AP) with subpopulations that differ in size and discharge probabilities. The mechanisms determining these discharge patterns remain unclear. This study investigated the hypothesis that variations in AP discharge are due to subpopulation-specific baroreflex control. We employed multi-unit microneurography and a continuous wavelet analysis approach to extract sympathetic APs in 12 healthy individuals during baseline (BSL) and lower body negative pressure (LBNP; -40, -60, -80 mmHg). For each AP cluster, the baroreflex threshold slope was measured from the linear regression between AP probability (%) and diastolic blood pressure (mmHg). During BSL, the baroreflex exerted non-uniform regulation over AP subpopulations: medium-sized AP clusters expressed the greatest slopes while clusters of small and large APs expressed weaker slopes. On going from BSL to LBNP, the baroreflex slopes for each AP subpopulation were modified differently. Baroreflex slopes (%/mmHg) for some medium APs (cluster 5: −4.4 ± 4 to −9.1 ± 5) expressed the greatest increase with LBNP, while slopes for large APs (cluster 9: −1.3 ± 1 to −2.6 ± 2) also increased, but to a lesser degree. Slopes for small APs present at BSL exhibited reductions with LBNP (cluster 2: −3.9 ± 3 to −2.2 ± 3). Larger previously silent AP clusters recruited with LBNP expressed weak baroreflex regulation (cluster 14: −0.9 ± 1%/mmHg). The baroreflex exerts the strongest control over medium-sized APs. Augmenting baroreflex gain and upward resetting of discrete AP subpopulations active at BSL, as well as recruiting larger previously silent APs with weak baroreflex control, facilitates elevated MSNA during orthostatic stress