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.

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.

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.

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.

scholarly journals Influence of Sex and Age on Muscle Sympathetic Nerve Activity of Healthy Normotensive Adults

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 997-1005 ◽  
Author(s):  
Daniel A. Keir ◽  
Mark B. Badrov ◽  
George Tomlinson ◽  
Catherine F. Notarius ◽  
Derek S. Kimmerly ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Body Mass ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Systematic Change ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Age Related

As with blood pressure, age-related changes in muscle sympathetic nerve activity (MSNA) may differ nonlinearly between sexes. Data acquired from 398 male (age: 39±17; range: 18–78 years [mean±SD]) and 260 female (age: 37±18; range: 18–81 years) normotensive healthy nonmedicated volunteers were analyzed using linear regression models with resting MSNA burst frequency as the outcome and the predictors sex, age, MSNA, blood pressure, and body mass index modelled with natural cubic splines. Age and body mass index contributed 41% and 11%, respectively, of MSNA variance in females and 23% and 1% in males. Overall, changes in MSNA with age were sigmoidal. At age 20, mean MSNA of males and females were similar, then diverged significantly, reaching in women a nadir at age 30. After 30, MSNA increased nonlinearly in both sexes. Both MSNA discharge and blood pressure were lower in females until age 50 (17±9 versus 25±10 bursts·min −1 ; P <1×10 −19 ; 106±11/66±8 versus 116±7/68±9 mm Hg; P <0.01) but converged thereafter (38±11 versus 35±12 bursts·min −1 ; P =0.17; 119±15/71±13 versus 120±13/72±9 mm Hg; P >0.56). Compared with age 30, MSNA burst frequency at age 70 was 57% higher in males but 3-fold greater in females; corresponding increases in systolic blood pressure were 1 (95% CI, −4 to 5) and 12 (95% CI, 6–16) mm Hg. Except for concordance in females beyond age 40, there was no systematic change with age in any resting MSNA-blood pressure relationship. In normotensive adults, MSNA increases after age 30, with ascendance steeper in women.

Stomach distension increases efferent muscle sympathetic nerve activity and blood pressure in healthy humans

1998 ◽  
Vol 161 (2) ◽  
pp. 148-155 ◽  
Author(s):  
P Rossi ◽  
G.I Andriesse ◽  
P.L Oey ◽  
G.H Wieneke ◽  
J.M.M Roelofs ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Nerve Activity ◽  
Healthy Humans

Naloxone does not affect the cardiovascular and sympathetic adjustments to static exercise in humans

1994 ◽  
Vol 77 (1) ◽  
pp. 231-235 ◽  
Author(s):  
C. A. Ray ◽  
J. A. Pawelczyk
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Static Exercise ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Double Blind ◽  
Endogenous Opiates ◽  
Muscle Ischemia

Previous studies suggested that endogenous opiates may attenuate the cardiovascular and sympathetic adjustments to static exercise. We tested whether this effect originates from exercising skeletal muscle. Eight men performed 2 min of static handgrip (30% maximum) followed by 2 min of posthandgrip muscle ischemia after three interventions: 1) control, 2) intra-arterial injection of naloxone HCl (60 micrograms) or vehicle (saline) in the exercising arm, and 3) systemic infusion of naloxone (4 mg) or vehicle. Naloxone and vehicle trials were performed double blind on separate days. Preexercise baseline muscle sympathetic nerve activity (burst frequency), heart rate, and blood pressure were similar across interventions on either day. During static handgrip, control, intra-arterial, and systemic administration of vehicle and naloxone elicited similar increases in total muscle sympathetic nerve activity (58 +/- 24 vs. 68 +/- 26, 146 +/- 49 vs. 132 +/- 42, 137 +/- 54 vs. 164 +/- 44%, respectively), heart rate (9 +/- 2 vs. 8 +/- 3, 16 +/- 3 vs. 16 +/- 2, 20 +/- 4 vs. 19 +/- 3 beats/min, respectively), and mean arterial pressure (22 +/- 4 vs. 21 +/- 4, 29 +/- 5 vs. 26 +/- 3, 28 +/- 4 vs. 27 +/- 4 mmHg, respectively). Additionally, there were no differences between vehicle and naloxone trials during posthandgrip muscle ischemia. Thus, contrary to previous reports, we conclude that the endogenous opiate peptide system does not modulate cardiovascular and sympathetic responses to brief periods of static exercise or muscle ischemia in humans.

Sympathetic Responses to Valsalva's Manoeuvre Following Bed Rest

2003 ◽  
Vol 28 (3) ◽  
pp. 342-355 ◽  
Author(s):  
J. Kevin Shoemaker ◽  
Cynthia S. Hogeman ◽  
Lawrence I. Sinoway
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Bed Rest ◽  
Pressure Control ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Head Up Tilt ◽  
Valsalva's Manoeuvre

The purpose of this study was to examine whether 14 days of head-down tilt bed rest (HDBR) alters autonomic regulation during Valsalva's manoeuvre (VM) and if this would predict blood pressure control during a 60° head-up tilt (HUT) test. To examine autonomic control of blood pressure, we measured the changes in systolic (ΔSBP) and diastolic (ΔDBP) blood pressure between baseline and the early straining (Phase IIE) period of VM (20 sec straining to 40 mmHg; N = 7) in conjunction with changes in muscle sympathetic nerve activity (MSNA; microneurography) burst frequency (B/min) and total activity (%Δ) from baseline over the 20-sec straining period. MSNA data were successfully recorded from 6 of the 7 individuals. The averaged responses from three repeated VMs performed in the supine position were compared between the pre- and post-HDBR tests. Compared with the pre-HDBR test, a greater reduction in SBP, DBP, and MAP was observed during Phase IIE following HDBR, p < 0.05. The increase in MSNA burst frequency during straining was augmented in the post- compared with the pre-HDBR test, p < 0.0001, as was the Phase IV blood pressure overshoot, p < 0.05. Although all subjects completed the 20-min pre-HDBR tilt test without evidence of hypotension or orthostatic intolerance, the post-HDBR test was stopped early in 5 of the 7 subjects due to systolic hypotension. The responses during the VM suggest that acute autonomic adjustments to rapid blood pressure changes are preserved after bed rest. Furthermore, MSNA and blood pressure responses during VM did not predict blood pressure control during orthostasis following HDBR. Key words: muscle sympathetic nerve activity, blood pressure, orthostatic tolerance, head-up tilt

GABAA receptor activation modulates the muscle sympathetic nerve activity responses at the onset of static exercise in humans

2021 ◽  
Author(s):  
André L. Teixeira ◽  
Igor A. Fernandes ◽  
Philip J. Millar ◽  
Lauro C. Vianna
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Stroke Volume ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Receptor Activation ◽  
Static Exercise ◽  
Nerve Activity ◽  
Exercise Onset

Exercise is a well-known sympathoexcitatory stimulus. However, muscle sympathetic nerve activity (MSNA) can decrease during the onset of muscle contraction. Yet, the underlying mechanisms and neurotransmitters involved in the sympathetic responses at the onset of exercise remain unknown. Herein, we tested the hypothesis that GABAA receptors may contribute to the MSNA responses at the onset of static handgrip in humans. Thirteen young, healthy individuals (4 females) performed 30 s of ischemic static handgrip at 30% of maximum volitional contraction before and following oral administration of either placebo or diazepam (10 mg), a benzodiazepine that enhances GABAA activity. MSNA (microneurography), beat-to-beat blood pressure (finger photopletysmography), heart rate (electrocardiogram) and stroke volume (ModelFlow) were continuously measured. Cardiac output (CO = stroke volume x heart rate) and total vascular conductance (TVC = CO / mean blood pressure) were subsequently calculated. At rest, MSNA was reduced while hemodynamic variables were unchanged after diazepam administration. Before diazepam, static handgrip elicited a significant decrease in MSNA burst frequency (∆-7±2 bursts/min, P<0.01 vs. baseline) and MSNA burst incidence (∆-16±2 bursts/100 heart beats, P<0.01 vs. baseline); however, these responses were attenuated following diazepam administration (∆-1±2 bursts/min and ∆-7±2 bursts/100 heart beats, respectively; P<0.01 vs. before diazepam). Diazepam did not affect the increases in heart rate, blood pressure, CO and TVC at the exercise onset. Importantly, the placebo had no effect on any variable at rest or exercise onset. These findings suggest that GABAA receptor activation modulates the MSNA responses at the onset of static exercise in young, healthy humans.

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.

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