Evidence for differential control of muscle sympathetic single units during mild sympathoexcitation in young, healthy humans

Abstract

Two subpopulations of muscle sympathetic single units with opposite discharge characteristics have been identified during low-level cardiopulmonary baroreflex loading and unloading in middle-aged adults and patients with heart failure. The present study sought to determine whether similar subpopulations are present in young healthy adults during cardiopulmonary baroreflex unloading ( study 1) and rhythmic handgrip exercise ( study 2). Continuous hemodynamic and multiunit and single unit muscle sympathetic nerve activity (MSNA) data were collected at baseline and during nonhypotensive lower body negative pressure (LBNP; n = 12) and 40% maximal voluntary contraction rhythmic handgrip exercise (RHG; n = 24). Single unit MSNA responses were classified as anticipated or paradoxical based on whether changes were concordant or discordant with the multiunit MSNA response, respectively. LBNP and RHG both increased multiunit MSNA burst frequency (∆5 ± 3 bursts/min, P < 0.001; ∆5 ± 8 bursts/min, P = 0.005), burst amplitude (∆5 ± 7%, P = 0.04; ∆13 ± 14%, P < 0.001), and total MSNA (∆302 ± 191 AU/min, P = 0.001; ∆585 ± 556 AU/min, P < 0.001). During LBNP and RHG, 43 and 64 muscle single units were identified, respectively, which increased spike frequency (∆9 ± 11 spikes/min, P < 0.001; ∆10 ± 19 spikes/min, P < 0.001) and the probability of multiple spike firing (∆10 ± 12%, P < 0.001; ∆11 ± 26%, P = 0.001). During LBNP and RHG, 36 (84%) and 39 (61%) single units possessed anticipated firing responses (∆12 ± 10 spikes/min, P < 0.001; ∆19 ± 19 spikes/min, P < 0.001), whereas 7 (16%) and 25 (39%) single units exhibited paradoxical reductions (∆−3 ± 1 spikes/min, P = 0.003; ∆−4 ± 5 spikes/min, P < 0.001). The observation of divergent subpopulations of muscle sympathetic single units in healthy young humans during two mild sympathoexcitatory stressors supports differential control at the fiber level as a fundamental characteristic of human sympathetic regulation. NEW & NOTEWORTHY The activity of muscle sympathetic single units was recorded during cardiopulmonary baroreceptor unloading and rhythmic handgrip exercise in young healthy humans. During both stressors, the majority of single units (84% and 61%) exhibited anticipated behavior concordant with the integrated muscle sympathetic response, whereas a smaller proportion (16% and 39%) exhibited paradoxical sympathoinhibition. These results support differential control of postganglionic muscle sympathetic fibers as a characteristic of human sympathetic regulation during mild sympathoexcitatory stress. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/differential-control-of-sympathetic-outflow-in-young-humans/ .

Arterial baroreflex regulation of muscle sympathetic nerve activity at rest and during stress

“…; Incognito et al . ). A high‐impedance tungsten microelectrode was inserted percutaneously into the common fibular nerve, with a low‐impedance reference microelectrode inserted 2–3 cm away underneath the surface of the skin.…”

“…; Incognito et al . ). MSNA burst frequency (bursts min –1 ), burst incidence (bursts 100 heartbeats –1 ), and burst height (% of peak height) were quantified.…”

“…Data were analysed retrospectively from 70 recording periods collected from 66 young healthy participants (26 female) who completed research studies in our laboratory for unrelated hypotheses (Coates et al 2018;Incognito et al 2018Incognito et al , 2019Notay et al 2018). Of the 26 women studied, 17 were tested during the early follicular phase or placebo phase of oral contraception (n = 10).…”

Evidence for a physiological role of pulmonary arterial baroreceptors in sympathetic neural activation in healthy humans

“…2013; Incognito et al . 2018). However, in contrast, when a stimulus is localised precisely to the left atria–pulmonary vein junction of anaesthetised dogs, atrial receptor activation has no effect on sympathetic efferent activity in lumbar nerves, which is an analogue of human MSNA (Karim et al .…”

“…2013, 2015; Incognito et al . 2018). Given the strong evidence from animal studies and supporting evidence in humans, we believe that a potential role for pulmonary arterial baroreceptors in sympathetic neural activation in humans requires investigation.…”