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

2019 ◽  
Vol 316 (1) ◽  
pp. H13-H23 ◽  
Author(s):  
Anthony V. Incognito ◽  
Connor J. Doherty ◽  
Massimo Nardone ◽  
Jordan B. Lee ◽  
Karambir Notay ◽  
...  
Keyword(s):  
Single Unit ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Single Units ◽  
Handgrip Exercise ◽  
Burst Frequency ◽  
Healthy Humans ◽  
Sympathetic Regulation ◽  
Cardiopulmonary Baroreflex ◽  
Differential Control

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/ .

Microneurographic evidence in healthy middle-aged humans for a sympathoexcitatory reflex activated by atrial pressure

2013 ◽  
Vol 305 (6) ◽  
pp. H931-H938 ◽  
Author(s):  
Philip J. Millar ◽  
Hisayoshi Murai ◽  
Beverley L. Morris ◽  
John S. Floras
Keyword(s):  
Single Unit ◽  
Sympathetic Neurons ◽  
Muscle Sympathetic Nerve Activity ◽  
Venous Pressure ◽  
Atrial Pressure ◽  
Single Units ◽  
Positive Pressure ◽  
Lower Body ◽  
Middle Aged ◽  
Healthy Humans

Atrial mechanoreceptors, stimulated by increased pressure or volume, elicit in healthy humans a net sympathoinhibitory response. The co-existence of an atrial reflex eliciting muscle sympathoexcitation has been postulated but undetected by conventional multi-unit muscle sympathetic nerve activity (MSNA). We hypothesized that in response to a selective increase in atrial pressure, single-unit MSNA would reveal a subpopulation of efferent sympathetic neurons with firing patterns opposite to the integrated multi-unit MSNA envelope. Multi- and single-unit MSNA recordings were acquired in eight healthy middle-aged subjects (age, 57 ± 8 years; body mass index, 25 ± 2 kg/m2) submitted to selective decreases or increases in atrial pressure by nonhypotensive lower body negative pressure (LBNP; −10 mmHg) or nonhypertensive lower body positive pressure (LBPP; +10 mmHg), respectively. Single-unit MSNA firing responses were classified as anticipated if spike frequency and incidence increased with LBNP or decreased with LBPP and paradoxical if they decreased with LBNP or increased with LBPP. LBNP decreased (3.2 ± 2.8 to 1.4 ± 3.1 mmHg, P < 0.01) and LBPP increased (3.3 ± 2.7 to 4.9 ± 2.8 mmHg, P < 0.01) estimated central venous pressure without affecting stroke volume, systemic pressure, or resistance. Multi-unit MSNA increased with LBNP (31 ± 17 to 38 ± 19 bursts/min, P < 0.01) and diminished with LBPP (33 ± 15 to 28 ± 15 bursts/min, P < 0.01). Of 21 single-units identified, 76% exhibited firing responses to both LBNP and LBPP concordant with multi-unit MSNA, whereas 24% demonstrated discordant or paradoxical responses. The detection of two subpopulations of single-units within the multi-unit MSNA recording, exhibiting opposite firing characteristics, establishes the first evidence in humans for the existence of an excitatory cardiac-muscle sympathetic reflex activated by increasing atrial pressure.

Muscle sympathetic single-unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: the role of sympathoexcitation magnitude

2021 ◽  
Author(s):  
Anthony V. Incognito ◽  
André L. Teixeira ◽  
Brooke M. Shafer ◽  
Massimo Nardone ◽  
Tyler D. Vermeulen ◽  
...  
Keyword(s):  
Single Unit ◽  
Muscle Sympathetic Nerve Activity ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Spike Frequency ◽  
Single Units ◽  
Response Patterns ◽  
Handgrip Exercise ◽  
Young Males ◽  
End Tidal

A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy, young males at baseline and during: 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O2: 47±3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA (D273±208 vs. D254±193 AU, P=0.84) and single-unit spike frequency (D8±10 vs. D12±13 spikes/min, P=0.12). Among 19 identified single units, the proportion of activated (47% vs. 68%) non-responsive (32% vs. 16%) and inhibited (21% vs. 16%) single units were not different between rhythmic handgrip and isocapnic hypoxia (P=0.42). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (7 activated, 1 non-responsive, and 1 inhibited during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (D595±282 AU, P<0.01) only 1 single unit was inhibited. These findings suggest that the proportion of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males.

Hypovolemia and MSNA discharge patterns: assessing and interpreting sympathetic responses

2003 ◽  
Vol 284 (4) ◽  
pp. H1198-H1204 ◽  
Author(s):  
D. S. Kimmerly ◽  
J. K. Shoemaker
Keyword(s):  
Frequency Response ◽  
Sympathetic Nerve ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Venous Pressure ◽  
Distribution Analysis ◽  
Burst Frequency ◽  
Burst Amplitude ◽  
Reflex Control ◽  
Discharge Patterns

We previously demonstrated that diuretic-induced hypovolemia resulted in an enhanced baroreflex-mediated increase in integrated muscle sympathetic nerve activity (MSNA) and vasomotor tone during lower body negative pressure (LBNP) ( Am J Physiol Heart Circ Physiol 282: H645–H655, 2002). The purpose of this study was to perform a retrospective analysis of these data and examine the ability of relative MSNA burst amplitude distributions to highlight differences in baseline sympathetic nerve discharge patterns. An additional purpose was to determine whether differential responses in MSNA burst frequency and burst amplitude affect conclusions regarding sympathetic reflex control. MSNA, stroke volume (SV, Doppler), and estimated central venous pressure (CVP, dependent arm technique) were measured during LBNP within the placebo (Normo) and diuretic (Hypo; 100 mg/day spironolactone for 3 days) conditions ( n = 8). Compared with Normo, MSNA burst frequency at rest was elevated, and there was a rightward shift in the median of the relative burst amplitude distribution ( P < 0.05) in Hypo. During LBNP, the larger rise in total MSNA during Hypo versus Normo was due to greater increases in relative burst amplitude with no difference in the burst frequency response. The MSNA burst frequency response to LBNP was shifted to a higher position on the same MSNA-CVP curve during Hypo compared with Normo. In contrast, the Hypo burst amplitude response was shifted to a new curve with a slope that was similar to the Normo relationship. These data support the use of probability distribution analysis to examine intraindividual differences in baseline and reflex-mediated increases in MSNA burst amplitude. Furthermore, the differential effect of hypovolemia on the responses of burst frequency and amplitude during graded LBNP suggests that burst frequency data alone may not adequately represent reflex control of sympathetic outflow.

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

1987 ◽  
Vol 63 (6) ◽  
pp. 2558-2562 ◽  
Author(s):  
R. G. Victor ◽  
W. N. Leimbach
Keyword(s):  
Negative Pressure ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Venous Pressure ◽  
Orthostatic Stress ◽  
Lower Body ◽  
Burst Frequency ◽  
Leg Muscles ◽  
A Value ◽  
Sympathetic Discharge

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.

scholarly journals The activity of a single muscle sympathetic vasoconstrictor nerve unit is affected by physiological stress in humans

2006 ◽  
Vol 290 (2) ◽  
pp. H853-H860 ◽  
Author(s):  
Hisayoshi Murai ◽  
Shigeo Takata ◽  
Michiro Maruyama ◽  
Manabu Nakano ◽  
Daisuke Kobayashi ◽  
...  
Keyword(s):  
Single Unit ◽  
Physiological Stress ◽  
Valsalva Maneuver ◽  
Muscle Sympathetic Nerve Activity ◽  
Maximum Voluntary Contraction ◽  
Voluntary Contraction ◽  
Accurate Information ◽  
Neural Firing ◽  
Handgrip Exercise ◽  
New Strategy

Recording of neural firing from single-unit muscle sympathetic nerve activity (MSNA) is a new strategy offering information about the frequency of pure sympathetic firing. However, it is uncertain whether and when single-unit MSNA would be more useful than multiunit MSNA for analysis of various physiological stresses in humans. In 15 healthy subjects, we measured single-unit and multiunit MSNA before and during handgrip exercise at 30% of maximum voluntary contraction for 3 min and during the Valsalva maneuver at 40 mmHg expiratory pressure for 15 s. Shapes of individual single-unit MSNA were proved to be consistent and suitable for further evaluation. Single-unit and multiunit MSNA exhibited similar responses during handgrip exercise. However, acceleration of neural firing determined from single-unit MSNA became steeper than multiunit MSNA during the Valsalva maneuver. During the Valsalva maneuver, unlike handgrip exercise, the distribution of multiunit burst between 0, 1, 2, 3, and 4 spikes was significantly shifted toward multiple spikes within a given burst ( P < 0.05). These results indicated that evaluation of single-unit MSNA could provide more detailed and accurate information concerning the role and responses of neuronal discharges induced by various physiological stresses in humans, especially amid intense sympathetic activity.

scholarly journals Altered firing pattern of single-unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure

2009 ◽  
Vol 587 (11) ◽  
pp. 2613-2622 ◽  
Author(s):  
Hisayoshi Murai ◽  
Masayuki Takamura ◽  
Michirou Maruyama ◽  
Manabu Nakano ◽  
Tatsunori Ikeda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Sympathetic Nerve ◽  
Single Unit ◽  
Firing Pattern ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Handgrip Exercise ◽  
Nerve Activity

scholarly journals Role of the carotid chemoreceptors in insulin-mediated sympathoexcitation in humans

2020 ◽  
Vol 318 (1) ◽  
pp. R173-R181 ◽  
Author(s):  
Jacqueline K. Limberg ◽  
Blair D. Johnson ◽  
Michael T. Mozer ◽  
Walter W. Holbein ◽  
Timothy B. Curry ◽  
...  
Keyword(s):  
Sympathetic Nerve Activity ◽  
Low Dose ◽  
Muscle Sympathetic Nerve Activity ◽  
Healthy Adults ◽  
Fat Free Mass ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Carotid Chemoreceptors ◽  
Healthy Humans

We examined the contribution of the carotid chemoreceptors to insulin-mediated increases in muscle sympathetic nerve activity (MSNA) in healthy humans. We hypothesized that reductions in carotid chemoreceptor activity would attenuate the sympathoexcitatory response to hyperinsulinemia. Young, healthy adults (9 male/9 female, 28 ± 1 yr, 24 ± 1 kg/m2) completed a 30-min euglycemic baseline followed by a 90-min hyperinsulinemic (1 mU·kg fat-free mass−1·min−1), euglycemic infusion. MSNA (microneurography of the peroneal nerve) was continuously measured. The role of the carotid chemoreceptors was assessed at baseline and during hyperinsulinemia via 1) acute hyperoxia, 2) low-dose dopamine (1–4 µg·kg−1·min−1), and 3) acute hyperoxia + low-dose dopamine. MSNA burst frequency increased from baseline during hyperinsulinemia ( P < 0.01). Acute hyperoxia had no effect on MSNA burst frequency at rest ( P = 0.74) or during hyperinsulinemia ( P = 0.83). The insulin-mediated increase in MSNA burst frequency ( P = 0.02) was unaffected by low-dose dopamine ( P = 0.60). When combined with low-dose dopamine, acute hyperoxia had no effect on MSNA burst frequency at rest ( P = 0.17) or during hyperinsulinemia ( P = 0.85). Carotid chemoreceptor desensitization in young, healthy men and women does not attenuate the sympathoexcitatory response to hyperinsulinemia. Our data suggest that the carotid chemoreceptors do not contribute to acute insulin-mediated increases in MSNA in young, healthy adults.

Attenuated cardiac baroreflex in men with presyncope evoked by lower body negative pressure

2001 ◽  
Vol 100 (3) ◽  
pp. 303-309 ◽  
Author(s):  
Duminda N. WIJEYSUNDERA ◽  
Gary C. BUTLER ◽  
Shin-ichi ANDO ◽  
Michael J. POLLARD ◽  
Peter PICTON ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Stroke Volume ◽  
Negative Pressure ◽  
Healthy Subjects ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Venous Pressure ◽  
Power Spectra ◽  
Lower Body ◽  
Burst Frequency

Mechanisms responsible for presyncope during lower body negative pressure (LBNP) in otherwise healthy subjects are poorly understood. Muscle sympathetic nerve activity (MSNA), blood pressure, heart rate (HR), HR power spectra, central venous pressure (CVP) and stroke volume were determined in 14 healthy men subjected to incremental LBNP. Of these, seven experienced presyncope at LBNP >-15 mmHg. Subjects who tolerated LBNP >-15 mmHg had significantly lower CVP (2.6±1.0 versus 7.2±1.2 mmHg; means±S.E.M., P < 0.02), HR (59±2 versus 66±3 beats/min, P < 0.05) and MSNA burst frequency (29.0±2.4 versus 39.0±3.5 bursts/min, P < 0.05) during supine rest. LBNP at -15 mmHg had no effect on blood pressure, but caused similar and significant reductions in stroke volume and cardiac output in both groups. Subjects who tolerated LBNP had significant reflex increases in HR, MSNA burst frequency and burst amplitude with LBNP of -15 mmHg. These responses were absent in those who experienced presyncope. The gain of the cardiac baroreflex regulation of MSNA was markedly attenuated in pre-syncopal subjects (1.2±0.6 versus 8.8±1.4 bursts/100 heart beats per mmHg; P < 0.001). Healthy subjects who experience presyncope in response to LBNP appear more dependent, when supine, upon MSNA to maintain preload, and less able to increase sympathetic vasoconstrictor discharge to skeletal muscle reflexively in response to orthostatic stimuli.

scholarly journals Lower-limb venous distension reflex and orthostatic tolerance in young healthy humans

2020 ◽  
Vol 319 (2) ◽  
pp. R142-R147
Author(s):  
Jian Cui ◽  
Cheryl Blaha ◽  
Michael D. Herr ◽  
Lawrence I. Sinoway
Keyword(s):  
Negative Pressure ◽  
Lower Limb ◽  
Sympathetic Nerve Activity ◽  
Lower Body Negative Pressure ◽  
Muscle Sympathetic Nerve Activity ◽  
Tolerance Test ◽  
Tolerance Index ◽  
Orthostatic Tolerance ◽  
Healthy Humans ◽  
Postural Stress

Earlier reports suggest that limb venous distension evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) (i.e., venous distension reflex). Our recent report also shows that suction of arterially occluded limb evokes venous distension reflex. We postulate that the venous distension reflex contributes to autonomic responses to orthostatic stress. In this study, we hypothesized that orthostatic tolerance would be linked to the MSNA response seen with lower limb suction. Fifteen healthy subjects were tested in the supine position. Negative pressure (−100 mmHg) was applied on an arterially occluded lower limb for 2 min. MSNA from the peroneal nerve in the limb not exposed to suction, ECG, and BP (Finometer) was recorded throughout the study. Limb occlusion without suction was used as a control trial. In a separate visit, the individual’s orthostatic tolerance was assessed using a graded lower body negative pressure (LBNP) tolerance test. Mean arterial BP and MSNA (18.6 ± 1.9 to 23.6 ± 2.0 bursts/min) significantly (both P < 0.05) increased during limb suction. Orthostatic tolerance index positively correlated ( R = 0.636, P = 0.011) with the MSNA response seen with suction during occlusion. Since the venous distension reflex strength correlates with the level of orthostatic tolerance, we speculate that lower-limb venous distension reflex engagement increases the sympathetic responses during orthostatic challenge and serves to maintain BP with postural stress.

Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans

2008 ◽  
Vol 295 (3) ◽  
pp. R891-R898 ◽  
Author(s):  
Friedhelm Sayk ◽  
Alexander Vietheer ◽  
Bernhard Schaaf ◽  
Peter Wellhoener ◽  
Gunther Weitz ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Blood Levels ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Healthy Humans ◽  
Vascular Bed

Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-α and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean ± SE: 12.1 ± 2.9 vs. 27.5 ± 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 ± 3.1 vs. 60.6 ± 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.

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