Leg Muscle Sympathetic Nerve Activity Research Articles

Heart failure-specific inverse relationship between the muscle sympathetic response to dynamic leg exercise and V̇O2peak

During 1-leg cycling, contralateral muscle sympathetic nerve activity (MSNA) falls in healthy adults but increases in most with reduced ejection fraction heart failure (HFrEF). We hypothesized that their peak oxygen uptake (V̇O2peak) relates inversely to their MSNA response to exercise. Twenty-nine patients (6 women; 63 ± 9 years; left ventricular ejection fraction: 30 ± 7%; V̇O2peak: 78 ± 23 percent age-predicted (%V̇O2peak); mean ± SD) and 21 healthy adults (9 women; 58 ± 7 years; 115 ± 29%V̇O2peak) performed 2min of mild- ("loadless") and moderate-intensity ("loaded") 1-leg cycling. Heart rate, blood pressure (BP), contralateral leg MSNA and perceived exertion rate (RPE) were recorded. Resting MSNA burst frequency (BF) was higher (p < 0.01) in HFrEF (51 ± 11 vs 44 ± 7 bursts·min-1). Exercise heart rate, BP and RPE responses at either intensity were similar between groups. In minute 2 of "loadless" and "loaded" cycling, group mean BF fell from baseline values in controls (-5 ± 6 and -7 ± 7 bursts·min-1, respectively) but rose in HFrEF (+5 ± 7 and +5 ± 10 bursts·min-1). However, in 10 of the latter cohort, BF fell, similarly to controls. An inverse relationship between ΔBF from baseline to "loaded" cycling and %V̇O2peak was present in patients (r = -0.43, p < 0.05) but absent in controls (r = 0.07, p = 0.77). In HFrEF, ∼18% of variance in %V̇O2peak can be attributed to the change in BF elicited by exercise. Novelty: Unlike healthy individuals, in the majority of heart failure patients with reduced ejection fraction (HFrEF), 1-leg cycling increases muscle sympathetic nerve activity (MSNA). In HFrEF, ∼18% of age-predicted peak oxygen uptake (V̇O2peak) can be attributed to changes in MSNA elicited by low-intensity exercise. This relationship is absent in healthy adults.

High-Intensity Interval Training Decreases Muscle Sympathetic Nerve Activity in Men With Essential Hypertension and in Normotensive Controls.

Exercise training is a cornerstone in reducing blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in individuals with essential hypertension. High-intensity interval training (HIIT) has been shown to be a time efficient alternative to classical continuous training in lowering BP in essential hypertension, but the effect of HIIT on MSNA levels has never been investigated. Leg MSNA responsiveness to 6 weeks of HIIT was examined in 14 hypertensive men (HYP; age: 62 ± 7 years, night time BP: 136 ± 12/83 ± 8 mmHg, BMI: 28 ± 3 kg/m2), and 10 age-matched normotensive controls (NORM; age: 60 ± 8 years, night time BP: 116 ± 2/68 ± 4 mmHg and BMI: 27 ± 3 kg/m2). Before training, MSNA levels were not different between HYP and NORM (burst frequency (BF): 41.0 ± 10.3 vs. 33.6 ± 10.6 bursts/min and burst incidence (BI): 67.5 ± 19.7 vs. 64.2 ± 17.0 bursts/100 heart beats, respectively). BF decreased (P < 0.05) with training by 13 and 5% in HYP and NORM, respectively, whereas BI decreased by 7% in NORM only, with no difference between groups. Training lowered (P < 0.05) night-time mean arterial- and diastolic BP in HYP only (100 ± 8 vs. 97 ± 5, and 82 ± 6 vs. 79 ± 5 mmHg, respectively). The change in HYP was greater (P < 0.05) compared to NORM. Training reduced (P < 0.05) body mass, visceral fat mass, and fat percentage similarly within- and between groups, with no change in fat free mass. Training increased (P < 0.05) V̇O2-max in NORM only. Six weeks of HIIT lowered resting MSNA levels in age-matched hyper- and normotensive men, which was paralleled by a significant reduction in BP in the hypertensive men.

Effect of aging on arm and leg muscle sympathetic nerve activity in humans

Aging is associated with heterogeneous changes in sympathetic nervous system outflow to various organs. Previous studies have consistently reported pronounced increases in leg muscle sympathetic activity (MSNA) at rest with age. We tested the hypothesis that aging is associated with similar increases in arm and leg MSNA at rest. Moreover, we tested the hypothesis that baroreflex unloading elicits similar increases in arm and leg MSNA in older adults. To address these hypotheses we simultaneously measured arm and leg MSNA using microneurography in young (N=7; 23±1 years old; mean±SE) and older adults (n=5: 63±2) at rest and in response to lower body negative pressure (LBNP of ‐10, ‐20, and ‐40 mmHg) (older subjects only). MSNA at rest increased similarly with age in the arm (8±2 vs. 34±6 bursts/min for young and older, respectively; P&lt;0.05) and leg (9±2 vs. 35±6 bursts/min; P&lt;0.05). Moreover, LBNP elicited similar increases in leg (Δ4±2, Δ8±4, and Δ16±6 bursts/min, change from baseline for ‐10, ‐20, and ‐40 mmHg LBNP, respectively; main effect P&lt;0.05) as well as arm MSNA (Δ4±2, Δ2±2, and Δ15±6; main effect P&lt;0.05) in older adults. Collectively, these data indicate that aging is associated with similar increases in arm and leg MSNA at rest. Moreover, parallel increases in leg and arm MSNA occur during baroreflex unloading in older humans.Support: NIH AG24420, HL77670, M01 RR10732

Sympathetic neural responses to mental stress: responders, nonresponders and sex differences

Mental stress consistently increases heart rate (HR) and blood pressure (BP) in humans, despite inconsistent sympathetic neural responses that include increases, decreases, or no change in muscle sympathetic nerve activity (MSNA). The purpose of the present study was to examine associations between MSNA, BP, and HR responses to mental stress. Leg MSNA, BP, HR, and perceived stress levels were recorded during 3-5 min of mental arithmetic in 82 subjects (53 men and 29 women). Subjects were divided into positive responders (>or=Delta3 bursts/min; n = 40), negative responders (<or=Delta-3 bursts/min; n = 9), and nonresponders (n = 33). Mental stress increased MSNA in positive responders (Delta6 +/- 1 bursts/min), decreased MSNA in negative responders (Delta-6 +/- 1 bursts/min), and did not change MSNA in nonresponders (Delta1 +/- 1 bursts/min). Mental stress increased mean BP and HR similarly in positive responders (Delta15 +/- 1 mmHg and Delta16 +/- 1 beats/min; P < 0.001), nonresponders (Delta15 +/- 1 mmHg and Delta19 +/- 2 beats/min; P < 0.001), and negative responders (Delta12 +/- 2 mmHg and Delta19 +/- 3 beats/min; P < 0.001). Perceived stress levels and sex distributions were similar across responders and nonresponders; thus, perceived stress and sex do not appear to influence MSNA during mental stress. However, men demonstrated higher increases of mean BP during mental stress when compared with women (Delta16 +/- 1 vs. Delta12 +/- 1 mmHg; P < 0.05), despite no differences in MSNA responses. In conclusion, our results demonstrate marked differences in MSNA responses to mental stress and a disassociation between MSNA and BP responses to mental stress, suggesting complex patterns of vascular responsiveness during mental stress.

Insufficient flow reduction during LBNP in both splanchnic and lower limb areas is associated with orthostatic intolerance after bedrest

We quantified the impact of a 60-day head-down tilt bed rest (HDBR) with countermeasures on the arterial response to supine lower body negative pressure (LBNP). Twenty-four women [8 control (Con), 8 exercise + LBNP (Ex-LBNP), and 8 nutrition (Nut) subjects] were studied during LBNP (0 to -45 mmHg) before (pre) and on HDBR day 55 (HDBR-55). Left ventricle diastolic volume (LVDV) and mass, flow velocities in the middle cerebral artery (MCA flow) and femoral artery (femoral flow), portal vein cross-sectional area (portal flow), and lower limb resistance (femoral resistance index) were measured. Muscle sympathetic nerve activity (MSNA) was measured in the fibular nerve. Subjects were identified as finishers or nonfinishers of the 10-min post-HDBR tilt test. At HDBR-55, LVDV, mass, and portal flow were decreased from pre-HDBR (P < 0.05) in the Con and Nut groups only. During LBNP at HDBR-55, femoral and portal flow decreased less, whereas leg MSNA increased similarly, compared with pre-HDBR in the Con, Nut, and NF groups; 11 of 13 nonfinishers showed smaller LBNP-induced reductions in both femoral and portal flow (less vasoconstriction), whereas 10 of 11 finishers maintained vasoconstriction in either one or both regions. The relative distribution of blood flow in the cerebral versus portal and femoral beds during LBNP [MCA flow/(femoral + portal flow)] increased or reduced < 15% from pre-HDBR in 10 of 11 finishers but decreased > 15% from pre-HDBR in 11 of 13 nonfinishers. Abnormal vasoconstriction in both the portal and femoral vascular areas was associated with orthostatic intolerance. The vascular deconditioning was partially prevented by Ex-LBNP.

Effect of gender on vestibular sympathoexcitation

Studies have suggested that premenopausal women are more prone to orthostatic intolerance than men. Additionally, it has been postulated that the vestibulosympathetic reflex is important in regulating postural-related changes in sympathetic activity. The purpose of the present study was to determine whether men and women differ in their sympathetic and cardiovascular responses to stimulation of the otolith organs elicited by head-down rotation (HDR). Heart rate (HR), arterial pressure, calf blood flow (CBF), and leg muscle sympathetic nerve activity (MSNA) were measured during 3 min of HDR in the prone posture in 33 women and 30 men. With the exception of HR (71 +/- 2 and 63 +/- 1 beats/min for women and men, respectively; P < 0.01), all baseline variables were not different between genders. There were no gender differences in responses to HDR. MSNA increased 72 +/- 33 units (43%) in the men and 88 +/- 15 units (59%) in the women during HDR (P < 0.01). CBF decreased [-0.6 +/- 0.1 (15%) and -0.5 +/- 0.1 (19%) ml. min(-1). 100 ml(-1)] and calf vascular resistance increased [8 +/- 2 (21%) and 11 +/- 3 (25%) units during HDR for men and women, respectively (P < 0.01)]. Both in the men and women, HR increased 2 +/- 1 beats/min (P < 0.01). These results demonstrate that sympathetic activation during HDR in the prone posture is similar in men and women. Therefore, these findings suggest that the vestibulosympathetic reflex is not different between healthy men and women.

Post–Apneic Inhalation Reverses Apnea-Induced Sympathoexcitation Before Restoration of Blood Oxygen Levels

Sleep apneas acutely increase sympathetic nerve activity (SNA) and thus arterial blood pressure. We hypothesized that after apnea, sympathoexcitation decreases before recovery of blood oxygen levels because of the predominant inhibitory effect respiratory factors exert over sympathetic nervous system activation. Seven healthy subjects were instrumented for arterial oxygen saturation (pulse oximetry, SaO2), leg muscle SNA (microneurography), and arterial pressure (Finapres). Supine subjects breathed 12% oxygen, 3% carbon dioxide, and 85% nitrogen for one min prior to apnea at the end of a normal tidal expiration. We accounted for circulatory delay in SaO2 measurement (5.4 +/- 0.4 s, mean +/- SE) as the time from the termination of apnea to the midpoint of the nadir of SaO2. SaO2 decreased to average 84 +/- 3% over the final 10 seconds of apnea, and recovered only partially to average 87 +/- 3% over the 10 seconds immediately following apnea. End-expiratory apnea increased SNA 14-fold from baseline levels of 217 +/- 37 units/10 seconds to 3063 +/- 442 units/10 seconds. However, SNA decreased to 93 +/- 32 units/10 s during the first 10 seconds after apnea. These findings indicate that sympathoinhibitory effects of respiratory signals, either lung inflation receptors or central respiratory inputs, predominate over sympathoexcitatory inputs from chemoreceptors to produce immediate and complete sympathoinhibition at the termination of a voluntary apnea. Arterial baroreflexes probably also contribute to sympathoinhibition after apnea.

Effect of concentric and eccentric muscle actions on muscle sympathetic nerve activity.

The purpose of this study was to determine the effects of concentric (Con) and eccentric (Ecc) muscle actions on leg muscle sympathetic nerve activity (MSNA). Two protocols were utilized. In protocol 1, eight subjects performed Con and Ecc arm curls for 2 min, with a resistance representing 50% of one-repetition maximum for Con curls. Heart rate (HR) and mean arterial pressure (MAP) were greater (P < 0. 05) during Con than during Ecc curls. Similarly, the MSNA was greater (P < 0.05) during Con than during Ecc curls. In protocol 2, eight different subjects performed Con and Ecc arm curls to fatigue, followed by postexercise muscle ischemia, by using the same resistance as in protocol 1. Endurance time was significantly greater for Ecc than for Con curls. The increase in HR, MAP, and MSNA was greater (P < 0.05) during Con than during Ecc curls. However, when the data were normalized as a function of endurance time, the differences in HR, MAP, and MSNA between Con and Ecc curls were no longer present. HR, MAP, and MSNA responses during postexercise muscle ischemia were similar for Con and Ecc curls. Con curls elicited greater increase (P < 0.05) in blood lactate concentration than did Ecc curls. In summary, Con actions contribute significantly more to the increase in cardiovascular and MSNA responses during brief, submaximal exercise than do Ecc actions. However, when performed to a similar level of effort (i.e., fatigue), Con and Ecc muscle actions elicit similar cardiovascular and MSNA responses. These results indicate that the increase in MSNA during a typical bout of submaximal dynamic exercise is primarily mediated by the muscle metaboreflex, which is stimulated by metabolites produced predominantly during Con muscle action.

THE EFFECT OF MUSCLE COMPRESSION DURING POSTHANDGRIP MUSCLE ISCHEMIA ON MUSCLE SYMPATHETIC NERVE ACTIVITY 778

It has been reported that forearm compression, which presumably activates the muscle mechanoreflex, augments muscle sympathetic nerve activity (MSNA) during isometric handgrip (IHG). The purpose of this study was to determine if forearm compression (FC) during posthandgrip muscle ischemia (PHGMI) would have an effect on MSNA. To test this question, leg MSNA, heart rate (HR), and mean arterial pressure (MAP) were measured during 3 min of IHG at 30% of maximal voluntary contraction followed by 2 min of PHGMI. PHGMI was elicited by inflating a pneumatic cuff to suprasystolic levels on the upper arm 5 seconds before the end of IHG. The subjects performed the protocol with and without forearm compression on the previously exercising arm during PHGMI. Forearm compression was elicited by inflating a pneumatic cuff around the forearm to 120 mmHg. The testing order was counterbalanced. The results were as follows (*p<0.01 vs. preexercise): Table Preexercise measurements were similar between trials for HR, MAP, and MSNA. IHG elicited characteristic increases in all variables, and PHGMI produced similar responses for both trials. None of the changes from IHG to PHGMI were significantly different between the two trials. We conclude that forearm compression during PHGMI does not alter HR, MAP, and MSNA responses. Thus, this study suggests that activation of the muscle mechanoreflex by forearm compression during PHGMI does not augment MSNA.

Muscle sympathetic nerve responses to static leg exercise.

Previous studies of muscle sympathetic nerve activity (MSNA) during static exercise have employed predominantly the arms. These studies have revealed striking increases in arm and leg MSNA during static handgrip (SHG) and postexercise circulatory arrest (PECA). The purpose of this study was to examine MSNA during static leg exercise (SLE) at intensities and duration commonly used during SHG followed by PECA. During 2 min of SLE (static knee extension) at 10% of maximal voluntary contraction (MVC; n = 18) in the sitting position, mean arterial pressure and heart rate increased significantly. Surprisingly, MSNA in the contralateral leg did not increase above control levels during SLE but rather decreased (23 +/- 5%; P < 0.05) during the 1st min of SLE at 10% MVC. We compared MSNA responses to SHG and SLE (n = 8) at 30% MVC. SHG and SLE elicited comparable increases (P < 0.05) in arterial pressure and heart rate, but SHG elicited significant increases in MSNA, whereas SLE did not. During PECA after SHG and SLE, mean arterial pressure remained significantly above control. However, MSNA was unchanged during PECA after SLE but was significantly greater than control during PECA after SHG. Because previous studies have indicated differences in MSNA responses to the arm and leg, we measured arm and leg MSNA simultaneously in six subjects during SLE at 20% MVC and PECA. During SLE and PECA, MSNA in the contralateral arm and leg did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxia potentiates exercise-induced sympathetic neural activation in humans

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O2 concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 +/- 3 (SE) beats/min; P less than 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 +/- 81 vs. 207 +/- 14% of control), PNE (175 +/- 25 vs. 120 +/- 11% of control), and heart rate (36 +/- 2 vs. 20 +/- 2 beats/min) were greater during hypoxia than during normoxia (P less than 0.05), whereas the arterial pressure response was not different (26 +/- 4 vs. 25 +/- 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P less than 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociation of sympathetic nerve activity in arm and leg muscle during mental stress.

Mental stress, which increases blood pressure and heart rate, increases forearm blood flow but does not change calf blood flow. The purpose of this study was to determine if mental stress increases muscle sympathetic nerve activity in the leg and causes a dissociation of muscle sympathetic nerve activity in the arm and the leg. We recorded heart rate, blood pressure, and efferent sympathetic nerve activity during mental stress (4 minutes of mental arithmetic) in 13 healthy men. Microelectrodes were inserted percutaneously into a fascicle of the peroneal nerve (leg) and radial nerve (arm) to measure sympathetic discharge to muscle. In Study 1, leg muscle sympathetic nerve activity was recorded in seven subjects. Mental stress significantly increased heart rate and blood pressure. Despite the increased blood pressure (which would be expected reflexly to inhibit sympathetic nerve activity), leg muscle sympathetic nerve activity (in total integrated activity, bursts per 100 heart beats or bursts per minute) increased significantly during stress. Further, whereas heart rate and blood pressure returned to normal during recovery, leg muscle sympathetic nerve activity remained elevated during recovery. In Study 2, simultaneous recordings were made of arm and leg muscle sympathetic nerve activity in six subjects. Mental stress increased heart rate and arterial pressure. Leg muscle sympathetic nerve activity again increased significantly during stress and remained elevated during recovery. In contrast, arm muscle sympathetic nerve activity did not change during stress. However, arm muscle sympathetic nerve activity increased significantly during recovery after stress. These studies indicate that a sympathoexcitatory influence of mental stress overrides or inhibits baroreceptor control of leg sympathetic nerve activity and stress causes a dissociation of arm and leg muscle sympathetic nerve activity with increased outflow to the leg but not to the arm. These observations may contribute to differences in blood flow to arm and leg during mental stress.