Microneurographic characterization of sympathetic responses during 1-leg exercise in young and middle-aged humans

Muscle sympathetic nerve activity (MSNA) at rest increases with age. However, the influence of age on MSNA recorded during dynamic leg exercise is unknown. We tested the hypothesis that aging attenuates the sympatho-inhibitory response observed in young subjects performing mild to moderate 1-leg cycling. After pre-determining peak oxygen uptake (VO2peak), we compared contra-lateral fibular nerve MSNA during 2 minutes each of mild (unloaded) and moderate (30-40% of the work rate at peak VO2, halved for single leg) 1-leg cycling in 18 young (23±1 years [mean±SE]) and 18 middle-aged (57±2 years) sex-matched healthy subjects. Mean height, weight, resting heart rate (HR), systolic blood pressure (BP) and percent predicted VO2peak were similar between groups. Middle-aged subjects had higher resting MSNA burst frequency and incidence (P<0.001) and diastolic BP (P=0.04). During moderate 1-leg cycling, older subjects’ systolic BP increased more (+21±5 vs.+10±1 mmHg; P=0.02) and their fall in MSNA burst incidence was amplified (-19±2 vs. -11±2 bursts/100heartbeats; P=0.01) but because HR rose less (+153 vs.+192 bpm; P=0.03), exercise induced similar reductions in burst frequency (P=0.25). Contrary to our initial hypothesis, with advancing age, mild to moderate intensity dynamic leg exercise elicits a greater rise in systolic BP and a larger fall in MSNA

Sex differences in blood pressure regulation during ischemic isometric exercise : the role of the β-adrenergic receptors

We sought to investigate whether the β-adrenergic receptors play a pivotal role in sex-related differences in arterial blood pressure (BP) regulation during isometric exercise. Sixteen volunteers (8 women) performed 2 min of ischemic isometric handgrip exercise (IHE) and 2 min of postexercise circulatory occlusion (PECO). Heart rate (HR) and beat-to-beat arterial BP were continuously measured. Beat-to-beat estimates of stroke volume (ModelFlow) were obtained and matched with HR to calculate cardiac output (Q̇) and total peripheral resistance (TPR). Two trials were randomly conducted between placebo and nonselective β-adrenergic blockade (40 mg propranolol). Under the placebo condition, the magnitude of the BP response in IHE was lower in women compared with men. During PECO, the BP remained elevated and the sex differences persisted. The β-blockade attenuated the BP response during IHE in men (∆57 ± 4 vs. ∆45 ± 7 mmHg, P = 0.025) due to a reduction in Q̇ (∆3.7 ± 0.5 vs. ∆1.8 ± 0.2 L/min, P = 0.012) while TPR was not affected. In women, however, the BP response during IHE was unchanged (∆27 ± 3 vs. ∆28 ± 3 mmHg, P = 0.889), despite attenuated Q̇ (∆2.7 ± 0.4 vs. ∆1.3 ± 0.2 L/min, P = 0.012). These responses were mediated by a robust increase in TPR under β-blockade (∆−0.2 ± 0.4 vs. ∆2.2 ± 0.7 mmHg·L−1·min, P = 0.012). These findings demonstrate that the sex differences in arterial BP regulation during ischemic IHE are mediated by β-adrenergic receptors

Cutaneous mechanoreceptor feedback from the hand and foot can modulate muscle sympathetic nerve activity

Stimulation of high threshold mechanical nociceptors on the skin can modulate efferent sympathetic outflow. Whether low threshold mechanoreceptors from glabrous skin are similarly capable of modulating autonomic outflow is unclear. Therefore, the purpose of this study was to examine the effects of cutaneous afferent feedback from the hand palm and foot sole on efferent muscle sympathetic nerve activity (MSNA). Fifteen healthy young participants (9 male; 25 ± 3 years [range: 22-29]) underwent microneurographic recording of multi-unit MSNA from the right fibular nerve during 2 minutes of baseline and 2 minutes of mechanical vibration (150Hz, 220μm peak-to-peak) applied to the left hand or foot. Each participant completed three trials of both hand and foot stimulation, each separated by 10 minutes. MSNA burst frequency decreased similarly during the two minutes of both hand (20.8 ± 8.9 vs. 19.3 ± 8.6 bursts/minute [ -8%], p=0.035) and foot (21.0 ± 8.3 vs. 19.5 ± 8.3 bursts/minute [ -8%], p=0.048) vibration but did not alter normalized mean burst amplitude or area (All p>0.05). Larger reductions in burst frequency were observed during the first 10 seconds (onset) of both hand (20.8 ± 8.9 vs. 17.0 ± 10.4 [ -25%], p<0.001) and foot (21.0 ± 8.3 vs. 18.3 ± 9.4 [ -16%], p=0.035) vibration, in parallel with decreases in normalized mean burst amplitude (hand: 0.45 ± 0.06 vs. 0.36 ± 0.14% [ -19%], p=0.03; foot: 0.47 ± 0.07 vs. 0.34 ± 0.19% [ -27%], p=0.02) and normalized mean burst area (hand: 0.42 ± 0.05 vs. 0.32 ± 0.12% [ -25%], p=0.003; foot: 0.47 ± 0.05 vs. 0.34 ± 0.16% [ -28%], p=0.01). These results demonstrate that tactile feedback from the hands and feet can influence efferent sympathetic outflow to skeletal muscle

Effects of muscle sympathetic burst size and burst pattern on time-to-peak sympathetic transduction

The current study evaluated the influence of resting muscle sympathetic nerve activity (MSNA) burst size and firing pattern on time-to-peak sympathetic transduction in 36 young healthy men and women. Participants underwent a 5-10 minute resting baseline with beat-to-beat measures of heart rate, mean arterial pressure (MAP), and MSNA (microneurography). Cardiac output and total vascular conductance were calculated using the Modelflow algorithm. Sympathetic transduction was quantified using the burst-triggered signal averaging technique, to examine the changes in MAP, cardiac output, and total vascular conductance for 15 cardiac cycles after each MSNA burst or non-burst. A stepwise increase in the peak MAP (i.e. sympathetic transduction) was observed throughout all quartiles of normalized MSNA burst area (Q1: 1.71.3 mmHg; Q2: 2.11.3 mmHg; Q3: 2.61.4 mmHg; Q4: 3.51.4 mmHg; PThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Case Studies in Physiology: Sympathetic neural discharge patterns in a healthy young male during end-expiratory breath hold-induced sinus pause

This case study reports the efferent muscle sympathetic nerve activity (MSNA) discharge patterns during a sinus pause observed during a maximal end-expiratory apnea in a young healthy male (age = 26 yr). During a 15.3-s end-expiratory apnea following a bout of intermittent hypercapnic hypoxia, we observed a 5.2-s (R-R interval) sinus pause and integrated MSNA recording, demonstrating a square-wave discharge pattern atypical of sharp MSNA burst peaks entrained to cardiac cycles or during preventricular contractions. This abnormal MSNA discharge pattern was observed again during a follow-up experiment, where an end-expiratory apnea at baseline resulted in pronounced bradycardia (R-R intervals \u3e2.5-s) but failed to reproduce the 5.2-s sinus pause. Action potential (AP) discharge patterns during MSNA bursts were detected using a continuous wavelet transform approach. AP discharge increased by 300% during the end-expiratory apnea with 5.2-s sinus pause compared with baseline and involved increased firing (i.e., rate-coding) of AP clusters (bins of AP with similar morphology) already present during baseline and pronounced recruitment of larger-amplitude AP clusters not present at baseline. Large-amplitude AP clusters continued to discharge during sinus pause. In summary, we show MSNA discharge during sinus pause and pronounced bradycardia during end-expiratory apnea, which demonstrates a square-wave discharge with recruitment of latent larger-amplitude AP clusters. The MSNA discharge was terminated before systole following sinus pause potentially through an inhibitory influence of inspiration, or cardiac mechanoreceptor feedback causing burst termination.NEW & NOTEWORTHY We characterize the occurrence of a square-wave discharge pattern of efferent muscle sympathetic nerve activity during a sinus pause in a young healthy male. This discharge pattern comprised large recruited action potential clusters undetected at baseline that continuously discharged during the sinus pause. Notably, this discharge pattern was still contained within a single cardiac cycle