We employed a novel action potential detection and classification technique to study the relationship between the recruitment of sympathetic action potentials (i.e., neurons) and the size of integrated sympathetic bursts in human muscle sympathetic nerve activity (MSNA). Multifiber postganglionic sympathetic nerve activity from the common fibular nerve was collected using microneurography in 10 healthy subjects at rest and during activation of sympathetic outflow using lower body negative pressure (LBNP). Burst occurrence increased with LBNP. Integrated burst strength (size) varied from 0.22 ± 0.07 V at rest to 0.28 ± 0.09 V during LBNP. Sympathetic burst size (i.e., peak height) was directly related to the number of action potentials within a sympathetic burst both at baseline (r = 0.75 ± 0.13; P < 0.001) and LBNP (r = 0.75 ± 0.12; P < 0.001). Also, the amplitude of detected action potentials within sympathetic bursts was directly related to the increased burst size at both baseline (r = 0.59 ± 0.16; P < 0.001) and LBNP (r = 0.61 ± 0.12; P < 0.001). In addition, the number of detected action potentials and the number of distinct action potential clusters within a given sympathetic burst were correlated at baseline (r = 0.7 ± 0.1; P < 0.001) and during LBNP (r = 0.74 ± 0.03; P < 0.001). Furthermore, action potential latency (i.e., an inverse index of neural conduction velocity) was decreased as a function of action potential size at baseline and LBNP. LBNP did not change the number of action potentials and unique clusters per sympathetic burst. It was concluded that there exists a hierarchical pattern of recruitment of additional faster conducting neurons of larger amplitude as the sympathetic bursts become stronger (i.e., larger amplitude bursts). This fundamental pattern was evident at rest and was not altered by the level of baroreceptor unloading applied in this study.

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 baroreflex-mediated 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 < 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 (R(2) = 0.98; P < 0.0001) and LBNP (R(2) = 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.

This study aimed to examine the effects of sex (males vs. females) and sex hormones (menstrual cycle phases in women) on sympathetic responsiveness to severe chemoreflex activation in young, healthy individuals. Muscle sympathetic nerve activity (MSNA) was measured at baseline and during rebreathing followed by a maximal end-inspiratory apnea. In women, baseline MSNA was greater in the midluteal (ML) than early-follicular (EF) phase of the menstrual cycle. Baseline MSNA burst incidence was greater in men than women, while burst frequency and total MSNA were similar between men and women only in the ML phase. Chemoreflex activation evoked graded increases in MSNA burst frequency, amplitude, and total activity in all participants. In women, this sympathoexcitation was greater in the EF than ML phase. The sympathoexcitatory response to chemoreflex stimulation of the EF phase in women was also greater than in men. Nonetheless, changes in total peripheral resistance were similar between sexes and menstrual cycle phases. This indicates that neurovascular transduction was attenuated during the EF phase during chemoreflex activation, thereby offsetting the exaggerated sympathoexcitation. Chemoreflex-induced increases in mean arterial pressure were similar across sexes and menstrual cycle phases. During acute chemoreflex stimulation, reduced neurovascular transduction could provide a mechanism by which apnea-associated morbidity might be attenuated in women relative to men.

T he risk of developing cardiovascular disease is lower in young women when compared with similarly aged men. [1][2][3] However, pregnancy represents a period of increased susceptibility to disordered cardiovascular regulation for women. Pregnant women have an elevated risk for orthostatic intolerance. 4,5 Moreover, ≤8% of pregnancies are associated with the development of de novo hypertension. 6 The cause of such hypertensive pregnancy disorders remains unclear, and as a result, there exist few approaches by which clinicians can predict, screen, or treat the development of the hypertensive disorders of pregnancy (gestational hypertension and preeclampsia). Previous data have shown that the vascular response to the cold pressor test (CPT) is blunted in normal pregnant women compared with women in the nonpregnant, postpartum state. 8 However, an elevated pressor response to the CPT has been observed in women with 9 or who subsequently develop 10 preeclampsia. As such, the CPT has been suggested as a simple screening tool for pregnancy-related hypertensive disorders. The mechanisms driving these divergent responses remain unknown; however, sympathetic nervous system activity is a primary determinant of the pressor response to the CPT. 11Differing vascular responses to the CPT may be mediated by altered sympathetic responses or altered translation of sympathetic activity into a vascular outcome (neurovascular transduction). Studies conducted over the past 2 decades have indicated, albeit not universally, 12 that normotensive Abstract-Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.

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