Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans

2008 ◽  
Vol 294 (2) ◽  
pp. R458-R466 ◽  
Author(s):  
Jian Cui ◽  
Vernon Mascarenhas ◽  
Raman Moradkhan ◽  
Cheryl Blaha ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Static Stretch ◽  
Wrist Extension ◽  
Healthy Humans ◽  
Metabolite Concentrations

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 ± 74 to 673 ± 90 U/min, P < 0.01) and mean blood pressure (102 ± 2 to 106 ± 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.

scholarly journals Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

2010 ◽  
Vol 299 (3) ◽  
pp. H925-H931 ◽  
Author(s):  
G. S. Gilmartin ◽  
M. Lynch ◽  
R. Tamisier ◽  
J. W. Weiss
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Chronic Intermittent Hypoxia ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Blood Pressure Elevation ◽  
Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

2001 ◽  
Vol 91 (4) ◽  
pp. 1679-1686 ◽  
Author(s):  
Jian Cui ◽  
Thad E. Wilson ◽  
Manabu Shibasaki ◽  
Nicole A. Hodges ◽  
Craig G. Crandall
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Arterial Blood ◽  
Muscle Ischemia ◽  
The Relationship

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative ( P < 0.001) during posthandgrip muscle ischemia (−201.9 ± 20.4 units · beat−1 · mmHg−1) when compared with control conditions (−142.7 ± 17.3 units · beat−1 · mmHg−1). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

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.

Modulation of sympathetic nerve activity during posthandgrip muscle ischemia in humans

1994 ◽  
Vol 266 (1) ◽  
pp. H79-H83 ◽  
Author(s):  
C. A. Ray ◽  
N. H. Secher ◽  
A. L. Mark
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Sensory Nerve ◽  
Vascular Occlusion ◽  
Voluntary Contraction ◽  
Central Command ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Muscle Ischemia

To evaluate modulation of muscle sympathetic nerve activity (MSNA) during posthandgrip muscle ischemia (PHGMI), subjects performed 2 min of isometric handgrip at 33% of maximal voluntary contraction (MVC) followed by 2 min of PHGMI produced by forearm vascular occlusion. The response to PHGMI was studied in the absence and again during the addition of contralateral rhythmic handgrip (RHG; 40 times/min) at 15% (n = 6) and 30% (n = 10) MVC during the second minute of the PHGMI. Additionally, to isolate the effect of central command, response to PHGMI was studied during attempted RHG after sensory nerve blockade (n = 5). RHG for 2 min at 15 and 30% MVC and attempted RHG for 2 min did not increase MSNA. Isometric handgrip elicited an 130 +/- 48% increase in MSNA (P < 0.05), which was maintained during PHGMI. RHG at 15 and 30% MVC elicited an attenuation of MSNA (-10 +/- 7% and -14 +/- 6%, respectively) when performed during the second minute of PHGMI (P < 0.05). In contrast, attempted RHG did not significantly affect MSNA during PHGMI. The findings demonstrate modulation of MSNA during activation of the muscle metaboreflex. The attenuation of metaboreceptor-mediated increases in MSNA appear to be the result of mechanosensitive muscle afferents and not central command.

scholarly journals Spontaneous bursts of muscle sympathetic nerve activity decrease leg vascular conductance in resting humans

2013 ◽  
Vol 304 (5) ◽  
pp. H759-H766 ◽  
Author(s):  
Seth T. Fairfax ◽  
Jaume Padilla ◽  
Lauro C. Vianna ◽  
Michael J. Davis ◽  
Paul J. Fadel
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Burst Size ◽  
Muscle Sympathetic Nerve Activity ◽  
Common Femoral Artery ◽  
Vascular Conductance ◽  
Nerve Activity ◽  
Arterial Blood

Previous studies in humans attempting to assess sympathetic vascular transduction have related large reflex-mediated increases in muscle sympathetic nerve activity (MSNA) to associated changes in limb vascular resistance. However, such procedures do not provide insight into the ability of MSNA to dynamically control vascular tone on a beat-by-beat basis. Thus we examined the influence of spontaneous MSNA bursts on leg vascular conductance (LVC) and how variations in MSNA burst pattern (single vs. multiple bursts) and burst size may affect the magnitude of the LVC response. In 11 young men, arterial blood pressure, common femoral artery blood flow, and MSNA were continuously recorded during 20 min of supine rest. Signal averaging was used to characterize percent changes in LVC for 15 cardiac cycles following heartbeats associated with and without MSNA bursts. LVC significantly decreased following MSNA bursts, reaching a nadir during the 6th cardiac cycle (single bursts, −2.9 ± 1.1%; and multiple bursts, −11.0 ± 1.4%; both, P < 0.001). Individual MSNA burst amplitudes and the total amplitude of consecutive bursts were related to the magnitude of peak decreases in LVC. In contrast, cardiac cycles without MSNA bursts were associated with a significant increase in LVC (+3.1 ± 0.5%; P < 0.001). Total vascular conductance decreased in parallel with LVC also reaching a nadir around the peak rise in arterial blood pressure following an MSNA burst. Collectively, these data are the first to assess beat-by-beat sympathetic vascular transduction in resting humans, demonstrating robust and dynamic decreases in LVC following MSNA bursts, an effect that was absent for cardiac cycles without MSNA bursts.

scholarly journals Disruption of phase synchronization between blood pressure and muscle sympathetic nerve activity in postural vasovagal syncope

2013 ◽  
Vol 305 (8) ◽  
pp. H1238-H1245 ◽  
Author(s):  
Christopher E. Schwartz ◽  
Elisabeth Lambert ◽  
Marvin S. Medow ◽  
Julian M. Stewart
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Phase Synchronization ◽  
Vasovagal Syncope ◽  
Muscle Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Control Subjects ◽  
Late Stages

Withdrawal of muscle sympathetic nerve activity (MSNA) may not be necessary for the precipitous fall of peripheral arterial resistance and arterial pressure (AP) during vasovagal syncope (VVS). We tested the hypothesis that the MSNA-AP baroreflex entrainment is disrupted before VVS regardless of MSNA withdrawal using the phase synchronization between blood pressure and MSNA during head-up tilt (HUT) to measure reflex coupling. We studied eight VVS subjects and eight healthy control subjects. Heart rate, AP, and MSNA were measured during supine baseline and at early, mid, late, and syncope stages of HUT. Phase synchronization indexes, measuring time-dependent differences between MSNA and AP phases, were computed. Directionality indexes, indicating the influence of AP on MSNA (neural arc) and MSNA on AP (peripheral arc), were computed. Heart rate was greater in VVS compared with control subjects during early, mid, and late stages of HUT and significantly declined at syncope ( P = 0.04). AP significantly decreased during mid, late, and syncope stages of tilt in VVS subjects only ( P = 0.001). MSNA was not significantly different between groups during HUT ( P = 0.700). However, the phase synchronization index significantly decreased during mid and late stages in VVS subjects but not in control subjects ( P < .001). In addition, the neural arc was significantly affected more than the peripheral arc before syncope. In conclusion, VVS is accompanied by a loss of the synchronous AP-MSNA relationship with or without a loss in MSNA at faint. This provides insight into the mechanisms behind the loss of vasoconstriction and drop in AP independent of MSNA at the time of vasovagal faint.

scholarly journals Heart rate variability and muscle sympathetic nerve activity response to acute stress: the effect of breathing

2010 ◽  
Vol 299 (1) ◽  
pp. R80-R91 ◽  
Author(s):  
Lindsay D. DeBeck ◽  
Stewart R. Petersen ◽  
Kelvin E. Jones ◽  
Michael K. Stickland
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Sympathetic Nerve ◽  
Spontaneous Breathing ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Cold Pressor ◽  
Isometric Handgrip ◽  
Nerve Activity ◽  
Controlled Breathing

Previous research has suggested a relationship between low-frequency power of heart rate variability (HRV; LF in normalized units, LFnu) and muscle sympathetic nerve activity (MSNA). However, investigations have not systematically controlled for breathing, which can modulate both HRV and MSNA. Accordingly, the aims of this experiment were to investigate the possibility of parallel responses in MSNA and HRV (LFnu) to selected acute stressors and the effect of controlled breathing. After data were obtained at rest, 12 healthy males (28 ± 5 yr) performed isometric handgrip exercise (30% maximal voluntary contraction) and the cold pressor test in random order, and were then exposed to hypoxia (inspired fraction of O2 = 0.105) for 7 min, during randomly assigned spontaneous and controlled breathing conditions (20 breaths/min, constant tidal volume, isocapnic). MSNA was recorded from the peroneal nerve, whereas HRV was calculated from ECG. At rest, controlled breathing did not alter MSNA but decreased LFnu ( P < 0.05 for all) relative to spontaneous breathing. MSNA increased in response to all stressors regardless of breathing. LFnu increased with exercise during both breathing conditions. During cold pressor, LFnu decreased when breathing was spontaneous, whereas in the controlled breathing condition, LFnu was unchanged from baseline. Hypoxia elicited increases in LFnu when breathing was controlled, but not during spontaneous breathing. The parallel changes observed during exercise and controlled breathing during hypoxia suggest that LFnu may be an indication of sympathetic outflow in select conditions. However, since MSNA and LFnu did not change in parallel with all stressors, a cautious approach to the use of LFnu as a marker of sympathetic activity is warranted.

Abstract 529: Muscle Sympathetic Nerve Activity is Higher in Winter than Other Seasons

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jian Cui ◽  
Matthew D Muller ◽  
Allen R Kunselman ◽  
Cheryl Blaha ◽  
Lawrence I Sinoway
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Epidemiological Data ◽  
Repeated Measurements ◽  
Nerve Activity ◽  
Cardiovascular Morbidity And Mortality ◽  
Significant Difference

Epidemiological data suggest that blood pressure tends to be higher in winter and lower in summer, particularly in the elderly. Moreover, hospitalization and mortality rates due to cardiovascular disease have higher rates in winter than summer. Whether autonomic adjustment including muscle sympathetic nerve activity (MSNA) varies with season is unclear. To test the hypothesis that resting MSNA varies along the seasons, we retrospectively analyzed the supine baseline (6 min) MSNA and heart rate (from ECG) of 57 healthy subjects (33M, 24F, 29 ± 1 yrs, range 22-64 yrs) from studies in our laboratory (room temperature ~23 °C). Each of these subjects from central Pennsylvania was studied during 2 or more seasons (total 231 visits). A linear-mixed effects model, which is an extension of the analysis of variance model accounting for repeated measurements (i.e. season) per subject, was used to assess the association of season with the cardiovascular outcomes. The Tukey-Kramer procedure was used to account for multiple comparisons testing between the seasons. MSNA burst rate in winter (21.3 ± 1.0 burst/min) was significantly greater than in summer (13.7 ± 1.0 burst/min, P < 0.001), spring (17.5 ± 1.6 burst/min, P = 0.04) and fall (17.0 ± 1.2 burst/min, P < 0.002). There was no significant difference in MSNA in other comparisons (spring vs. summer, P = 0.12; spring vs. fall, P = 0.99; summer vs. fall, P = 0.054). Heart rate (63.6 ± 1.1 vs. 60.8 ± 1.2 beats/min, P = 0.048) was significantly greater in winter compared to summer. Blood pressure (automated sphygmomanometry of the brachial artery) was not significantly different between seasons. The results suggest that baseline sympathetic nerve activity varies along the seasons, with peak levels evident in winter. We speculate that the seasonal MSNA variation may contribute to seasonal variations in cardiovascular morbidity and mortality.

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