J Appl Physiol 110: 670–680, 2011.
First published December 30, 2010; doi:10.1152/japplphysiol.00740.2010.
Differential contribution of central command to the cardiovascular responses
during static exercise of ankle dorsal and plantar flexion in humans
Nan Liang,1,2 Tomoko Nakamoto,1 Seina Mochizuki,1 and Kanji Matsukawa1,2
1
Department of Physiology, Graduate School of Health Sciences, and 2Center for Advanced Practice and Research
of Rehabilitation, Hiroshima University, Minami-ku, Hiroshima, Japan
Submitted 30 June 2010; accepted in final form 27 December 2010
autonomic nervous system; cardiovascular response; exercise pressor
reflex; lower limb
(HR) and arterial blood pressure
(AP) during voluntary static exercise are controlled by central
and peripheral mechanisms. Differential cardiovascular responses have been observed owing to muscular contraction,
with different force development, muscle mass, muscle fiber
composition, and training state (11, 12, 28 –30, 37, 42), suggesting a muscle-dependent peripheral effect on the cardiovascular responses. This may reflect that group III and IV muscle
thin-fiber afferents, which are sensitive to mechanical and
metabolic stimuli, respectively, are activated differentially,
depending on the muscle characteristics, and, consequently,
contribute differently to exercise pressor reflex.
Apart from the peripheral reflex mechanism, there is a
possibility that differential contribution of central command is
reserved for different cardiovascular responses to static exercise, as well as that of motor command for different motor
THE RESPONSES OF HEART RATE
Address for reprint requests and other correspondence: K. Matsukawa, Dept. of
Physiology, Graduate School of Health Sciences, Hiroshima Univ., 1-2-3 Kasumi,
Minami-ku, Hiroshima 734-8551, Japan (e-mail: [email protected]).
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activities. In fact, the strength of corticomotoneuronal connections with the human upper limb muscles is greater than that
with the lower limb muscles (4) and is also greater with the
distal muscles than that with the proximal muscles (8, 32).
Within the lower limb, motoneurons of the tibialis anterior
(TA) muscle receive a greater excitatory influence from the
primary motor cortex than those of the triceps surae (TS)
muscle, which is known as an antigravity muscle in the lower
limb and plays a role in unconscious postural control during
standing and walking (2, 5, 6, 38). These findings suggest that
a motor task, in which precise control is needed, accompanies
the greater and stronger control by central command, whereas
a motor task, which may be performed under unconscious
control and probably mediated by neural circuits at the subcortical level, accompanies the smaller and weaker control by
central command. If central command involves parallel activation of the motor and autonomic circuits in the central
nervous system (16), namely, the central motor and cardiovascular command interact with each other, it seems possible that
the cardiovascular responses to static exercise are modulated,
depending on the strength of central control in different motor
tasks. Indeed, Tokizawa et al. (37) showed that, when the force
was matched at 30% of the maximum voluntary contraction
(MVC) for 2 min, the increases of HR and AP at the end of
voluntary ankle dorsal flexion and during postexercise ischemia were larger than those during ankle plantar flexion.
Although the difference in the cardiovascular responses during
postexercise ischemia might be attributed to differential activation of the muscle metabosensitive reflex, the different
cardiovascular responses during voluntary exercise with different muscle groups, particularly at the beginning of exercise,
will be produced, depending on the strength of central control.
In the present study, we encouraged the subjects to perform
two kinds of voluntary static exercise: the right ankle dorsal or
plantar flexion. The agonist muscles for the exercise are the TA
and TS muscles, respectively, of which the difference in the
strength of motor command onto the two motoneuron pools has
been determined (2, 4 – 6, 38). The electrically induced involuntary static exercise was applied to detect the sole effects of
the muscle reflex on the cardiovascular responses without
central command. The recent findings using conscious animals
in our laboratory (23, 24, 25) supported the view that central
command, but not the peripheral muscle reflex, plays a predominant role in mediating the cardiovascular responses to
static exercise in the conscious condition, particularly during a
low intensity of exercise, like daily living. We hypothesized,
therefore, that HR and AP increase similarly during involuntary exercise of dorsal and plantar flexion, while those behave
differently during voluntary exercise, depending on the
strength of the cortical and subcortical connections. In other
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Liang N, Nakamoto T, Mochizuki S, Matsukawa K. Differential
contribution of central command to the cardiovascular responses
during static exercise of ankle dorsal and plantar flexion in humans. J
Appl Physiol 110: 670 – 680, 2011. First published December 30, 2010;
doi:10.1152/japplphysiol.00740.2010.—To examine whether central
command contributes differently to the cardiovascular responses during voluntary static exercise engaged by different muscle groups, we
encouraged healthy subjects to perform voluntary and electrically
evoked involuntary static exercise of ankle dorsal and plantar flexion.
Each exercise was conducted with 25% of the maximum voluntary
force of the right ankle dorsal and plantar flexion, respectively, for 2
min. Heart rate (HR) and mean arterial blood pressure (MAP) were
recorded, and stroke volume, cardiac output (CO), and total peripheral
resistance were calculated. With voluntary exercise, HR, MAP, and
CO significantly increased during dorsal flexion (the maximum increase, HR: 12 ⫾ 2.3 beats/min; MAP: 14 ⫾ 2.0 mmHg; CO: 1 ⫾ 0.2
l/min), whereas only MAP increased during plantar flexion (the
maximum increase, 6 ⫾ 2.0 mmHg). Stroke volume and total peripheral resistance were unchanged throughout the two kinds of voluntary
static exercise. With involuntary exercise, there were no significant
changes in all cardiovascular variables, irrespective of dorsal or
plantar flexion. Furthermore, before the force onset of voluntary static
exercise, HR and MAP started to increase without muscle contraction,
whereas they had no significant changes with involuntary exercise at
the moment. The present findings indicate that differential contribution of central command is responsible for the different cardiovascular
responses to static exercise, depending on the strength of central
control of the contracting muscle.
CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
words, the central command rather than the peripheral reflex
may play a predominant role in mediating the cardiovascular
responses to voluntary static exercise.
METHODS
J Appl Physiol • VOL
Netherlands). Assuming a nonlinear three-element model of aortic
input impedance, the software computed aortic blood flow from the
AP waveform (41). The reliability of the data of CO obtained from
this noninvasive method has been confirmed in the literature (22, 33,
35, 36).
Electrically evoked static exercise. Electrical muscle stimulation
(EMS) has been widely used to evoke involuntary static exercise (7,
10, 13, 14). Conventional transcutaneous EMS with repetitive electrical rectangular pulses at 60 Hz elicits tetanic muscle contraction,
which, in turn, may activate mechanoreceptors and metaboreceptors
in the contracting muscle. Moreover, the EMS may activate cutaneous
receptors, possibly causing a cardiovascular reflex response during the
involuntary static exercise.
To identify the sole effects of the exercise pressor reflex, we
utilized a low-frequency modulated electrical stimulation (LFS) (carrier frequency, 5.00 kHz; interference frequency, 4.94 kHz; modulated frequency, 60 Hz) with an electrotherapy unit for rehabilitation
(ES-510, Ito, Tokyo, Japan). Since skin impedance is relatively lower
with the LFS, deeper muscular tissue is expected to be more efficiently stimulated. To identify a difference in the cardiovascular
responses to electrically evoked involuntary static exercise between
the LFS and conventional EMS, in the preliminary experiment II (n ⫽
8 subjects), we attached a pair of stimulating electrodes (square form,
5 ⫻ 5 cm, Ito) to the right TS and then stimulated the muscle with LFS
and conventional EMS (frequency: 60 Hz, pulse width: 50 ␮s). The
output force level was adjusted for 25% MVC in the two modes of
involuntary static exercise. The results of the stimulating intensity,
output force, and cardiovascular responses during 2-min electrically
evoked plantar flexion are compared between the two modes of
electrical stimulation (LFS vs. EMS) in Fig. 2. With LFS, the intensity
for the sensory and motor threshold and for producing a force of 25%
MVC was lower than the intensity with EMS (Fig. 2, A and B).
Furthermore, the increases of HR and MAP were significantly lower
with LFS than those with EMS (Fig. 2, C and D), although the output
force was kept at 25% MVC (Fig. 2E). Thus it is suggested that the
excessive increases in HR and MAP during involuntary static exercise
with the conventional EMS involved an additional effect, except
exercise pressor reflex, which was at least partly avoided by using the
LFS.
In the main experiment, therefore, the LFS was utilized for evoking
the electrically evoked tetanic muscle contraction. Two pairs of
stimulating electrodes were attached to the right TA and TS muscles,
by which the right ankle dorsal and plantar flexion could be evoked,
respectively.
Experimental protocols. At the beginning of the main experiment,
the force level of 25% MVC was calculated and displayed on a
computer’s screen for confirmation. For voluntary contraction, the
subjects were asked to start performing static dorsal or plantar flexion
with the targeted force (25% MVC) at any time after a cue and then
keep the static exercise for 2 min with a visual feedback of the force
level. For electrically evoked involuntary contraction, the LFS was
utilized to induce the exercise at the same intensity for 2 min. The
stimulus intensity was increased smoothly and gradually for minimizing a startling effect on the cardiovascular responses and was adjusted
slightly so as to maintain the 25% MVC. A total of four protocols for
2 min were performed with the different muscle (the TA or TS
muscle) and different contraction type (voluntary and involuntary
exercise). To avoid muscle fatigue, each protocol was carried out
when the subject took rest sufficiently (interprotocol interval, 13 ⫾ 1
min), and the voluntary and involuntary protocols were performed in
an interleaved manner. The Borg rating of perceived exertion (RPE)
scale, according to the Borg 6 –20 unit scale (3), with which the
subject was asked about the “intensity” of each exercise, was measured 60 s after each session was accomplished. The visual analog
scale (VAS) pain (VASpain) score (0 –10 unit scale: 0, no pain; 1–3,
little; 4 – 6, small to medium; 7–9, hard; 10, the hardest) was also
asked at the same time.
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Subjects. A total of 13 healthy volunteers (eight men and five
women; age, 24 ⫾ 0.6 yr; height, 169 ⫾ 3.0 cm; body weight, 60 ⫾
2.1 kg), who did not suffer from any known cardiovascular and
neuromuscular diseases, participated in the present study. Five (men)
of the 13 subjects participated in the preliminary experiment I, 8 (4
men and 4 women) in the preliminary experiment II, and 10 (6 men
and 4 women) in the main experiment. Five of the 13 subjects
participated in both preliminary experiment I and the main experiment, and other five in both experiment II and the main experiment.
The experimental procedures and protocols were performed in accordance with the Declaration of Helsinki and approved by the Institutional Ethical Committee. All subjects gave their informed, written
consent before the experiments.
Static exercise of ankle dorsal and plantar flexion. The subjects lay
down in the supine position on a comfortable reclining seat of a cycle
ergometer (Strength Ergo 240 BK-ERG-003, Mitsubishi Electric Engineering, Tokyo, Japan), of which the torque against the wheel shaft
arisen from the pedals could be measured continuously (Fig. 1A). The
left and right cranks and pedals of the ergometer were all set in a fixed
mode, which enabled the subjects to put their feet on the cleated shoes
fitted on the pedals and then to generate static exercise of dorsal or
plantar flexion of the right ankle joint. The positions of the cranks,
pedals, and seat were adjusted for allowing the subjects to remain in
a comfortable and certain posture. The subjects were asked to perform
all bouts of static exercise by the right lower limb (hip and knee joint,
45° of flexion; ankle joint, 0° of plantar/dorsal flexion) and to relax the
left lower limb (hip and knee joint, 0° of flexion/extension; ankle
joint, relaxing) throughout the experiments. The force generated by
the right ankle dorsal or plantar flexion was assessed by the torque
arisen from the right pedal and recorded with a personal computer at
a sampling frequency of 10 Hz (Mitsubishi Electric Engineering,
Tokyo, Japan). The force during the MVC of dorsal and plantar
flexion was measured. For matching the level of muscle activation
between voluntary and involuntary exercise, great care was taken to
instruct the subject to perform the exercise with the right foot alone.
We confirmed in the preliminary experiment I (n ⫽ 5 subjects) that
electromyogram activity (band-pass filter 30 –500 Hz, multichannel telemetry system, WEB-7000, Nihon Kohden, Tokyo, Japan)
was restricted to the agonist muscle (TA and TS muscle, respectively) during voluntary exercise of dorsal and plantar flexion (Fig.
1, B and C).
Cardiovascular recordings. A pair of electrodes (Magnerode, TE18M-3, Fukuda Denshi, Tokyo, Japan) and a ground electrode were
attached on the chest for measurement of electrocardiogram (ECG).
The ECG signal and respiratory movement were monitored with a
telemetry system (DynaScope DS-3140, Fukuda Denshi, Tokyo, Japan). A blood pressure cuff was attached to the middle finger of the
left hand for noninvasively and continuously recording AP with a
Finometer (Finapres Medical Systems BV, Arnhem, the Netherlands).
ECG and AP were simultaneously fed to a computer at a sampling
frequency of 1 kHz (PowerLab system, AD Instruments Pty) for
off-line analysis. At the beginning of the experiments, blood pressure
assessed by the Finometer was corrected by return flow calibration,
using AP recorded in the left upper arm by a sphygmomanometric
auscultation method. The AP waveform was sampled with the Finometer at a frequency of 200 Hz, and then the beat-to-beat AP
response involving systolic, diastolic, and mean arterial blood pressure (MAP) and HR were calculated. Moreover, we simultaneously
assessed the beat-to-beat values of cardiac output (CO), stroke volume
(SV), and total peripheral resistance (TPR) by using a Modelflow
software (BeatScope 1.1, Finapres Medical Systems BV, Arnhem, the
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
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Fig. 1. A: an illustration of the experimental setup. The subjects performed static exercise of dorsal and plantar flexion with the right ankle joint in a certain
position, while the left lower limb was relaxing. Two pairs of the squares in the right lower limb show the stimulating electrodes used for evoking involuntary
exercise. The torque against the wheel shaft arisen from the right pedal (length 0.17 m) and the output force were measured. B and C: the electromyogram (EMG)
activities of four [tibialis anterior, triceps surae (TS), rectus femoris, and biceps femoris] muscles in the right lower limb were recorded during voluntary exercise
of dorsal and plantar flexion, for 2 min, in the preliminary experiment I. B: the specimen recordings of EMG activity from an individual subject. C: the integrated
EMG activities in the time course (in 10-s steps) from the subjects tested (n ⫽ 5). MVC, maximum voluntary contraction.
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
673
Data analysis. The onset of the 2-min static exercise was defined
as the time point at which the target force was kept as shown in
Fig. 3. The output force during the 2-min static exercise was
determined by the mean value averaged over the period. HR, MAP,
SV, CO, and TPR were continuously measured throughout the
experiments. Each baseline value at the resting state was determined as the average for 30 s before the start cue of the voluntary
exercise or the electrical stimulation. All parameters were then
expressed as the relative changes from the baseline. In the time
course data, the values over 30 s before and 20 s after the force
onset were calculated at 1-s intervals, and thereafter they were
calculated at 10-s intervals as averages over 10 s immediately
before each time point.
Statistical analysis. The torque and force were compared by a
paired t-test with Holm’s sequential Bonferroni correction (19)
among four different exercise protocols with different contraction
types (voluntary and involuntary) and different exercise directions
(dorsal and plantar flexion). In involuntary protocols, the stimulating intensities for inducing the 25% MVC and for the sensory
and motor threshold were compared between dorsal and plantar
flexion using a Student’s paired t-test. With the cardiovascular
parameters of HR, MAP, SV, CO, and TPR in the time course data,
a two-way ANOVA with repeated measures was used to examine
a difference in the values between dorsal and plantar flexion
(within-subject factor) in the voluntary and involuntary protocols,
respectively. Also, to reveal the significant changes from the
baseline, a one-way ANOVA with repeated measures followed by
a post hoc test of Dunnett was performed in an individual protocol.
The comparison of the Borg RPE scale and VASpain score among
the protocols was conducted by using a Wilcoxon matched-pairs
test. Moreover, the correlation analyses of the cardiovascular
responses with Borg RPE scale or VASpain score were performed
by using Spearman’s rank correlation. The level of statistical
significance was defined as P ⬍ 0.05. All values are expressed as
means ⫾ SE.
J Appl Physiol • VOL
RESULTS
The output force and stimulating intensity. The torque and
force during MVC and during 25% MVC of dorsal and plantar
flexion with the voluntary and electrically evoked involuntary
exercise, as well as the stimulating intensity used for the
involuntary exercise, are summarized in Table 1. The torque
and absolute force at the MVC with plantar flexion were much
greater than those with dorsal flexion. Since the relative output
force for each exercise was adjusted at the same 25% level
against the MVC, there were no significant differences in the
relative intensity of static exercise between dorsal and plantar
flexion in the voluntary and involuntary condition. The sensory
threshold between the involuntary conditions was similar,
while the electrical stimulation intensity needed for inducing
25% MVC of dorsal flexion was larger than that for plantar
flexion. The time interval from the force onset to the 25%
MVC was 5 ⫾ 0.3 and 5 ⫾ 0.6 s with voluntary dorsal and
plantar flexion, and 12 ⫾ 2.2 and 13 ⫾ 1.7 s with involuntary
dorsal and plantar flexion, respectively; in the involuntary
condition, the time interval from the sensory threshold to the
force onset was 15 ⫾ 1.2 and 16 ⫾ 0.9 s with dorsal and
plantar flexion, respectively (as indicated in Fig. 5). Thus no
significant difference in the temporal parameters was found
between the dorsal and plantar flexion with voluntary or
involuntary exercise.
VASpain and Borg scale scores. The VASpain score was zero
in all subjects in the voluntary condition (Table 1). There was
no significant difference in the VASpain score between dorsal
and plantar flexion (5 ⫾ 0.6 and 4 ⫾ 0.5 points, respectively;
corresponding to “small to medium”) in the involuntary condition, suggesting that the amount of afferents, including the
pain fibers stimulated, was small and similar between dorsal
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Fig. 2. A: relationship between the output force of
plantar flexion and a stimulating intensity during the
low-frequency stimulation (LFS) and the conventional electrical muscle stimulation (EMS) (n ⫽ 8).
B: the stimulating electrodes were attached to the TS
muscle of the right lower limb. Note that the minimum intensity that the subjects could perceive (sensory threshold), the minimum intensity needed to
generate a force (motor threshold), and the intensity
needed to generate a force of 25% of MVC (%MVC)
were lower with LFS than those with EMS. C and D:
the maximum increases of heart rate (HR; C) and
mean arterial blood pressure (MAP; D) when maintaining the 2-min involuntary exercise with LFS and
EMS. E: the force levels. *P ⬍ 0.05. **P ⬍ 0.01.
N.S., no significance.
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
and plantar flexion. Regarding the Borg scale score, there was
no difference between the dorsal and plantar flexion in the
involuntary condition. In contrast, in the voluntary condition,
the score was significantly higher with dorsal flexion than with
plantar flexion. A significant difference was also detected in
the Borg scale score with the dorsal flexion between the
voluntary and involuntary conditions (Table 1).
The cardiovascular responses to static exercise. The representative recordings of HR, AP, and output torque during
voluntary and involuntary static exercise obtained from an
individual subject are shown in Fig. 3. In the voluntary condition, HR and AP increased with dorsal flexion, but they did
not change substantially with plantar flexion, although the
absolute value of output force with plantar flexion was greater
Table 1. Torques, forces, stimulating intensity, scores of subjective index, and baseline values
Voluntary Exercise
TorqueMVC, N 䡠 m
ForceMVC, N
Torquedeveloped, N 䡠 m
Forcedeveloped, N
Force, %MVC
Sensory threshold, mA
Motor threshold, mA
Stimulating intensity, mA
VASpain score, points
Borg scale score, points
Baseline values
HR, beats/min
MAP, mmHg
SV, ml
CO, l/min
TPR, mmHg 䡠 ml⫺1 䡠 s⫺1
Involuntary Exercise
Dorsal
Plantar
31 ⫾ 3.1*
180 ⫾ 18.5*
8 ⫾ 1.1*
46 ⫾ 6.7*
25 ⫾ 2.4
62 ⫾ 3.5
365 ⫾ 20.4
17 ⫾ 0.9
100 ⫾ 5.1
28 ⫾ 1.0
0
13 ⫾ 0.7*†
0
9 ⫾ 0.5
63 ⫾ 3.6
93 ⫾ 2.6
84 ⫾ 4.5
5.3 ⫾ 0.5
1.1 ⫾ 0.1
65 ⫾ 3.3
92 ⫾ 3.4
86 ⫾ 4.9
5.6 ⫾ 0.4
1.0 ⫾ 0.1
Dorsal
Plantar
7 ⫾ 0.9*
42 ⫾ 5.1*
24 ⫾ 2.7
13 ⫾ 1.5
37 ⫾ 3.5
72 ⫾ 6.5*
5 ⫾ 0.6
9 ⫾ 0.9
17 ⫾ 0.8
97 ⫾ 4.5
27 ⫾ 1.7
12 ⫾ 1.2
31 ⫾ 2.3
56 ⫾ 5.9
4 ⫾ 0.5
9 ⫾ 0.8
63 ⫾ 3.0
94 ⫾ 2.8
84 ⫾ 4.0
5.3 ⫾ 0.3
1.1 ⫾ 0.1
65 ⫾ 4.0
94 ⫾ 3.0
84 ⫾ 4.9
5.4 ⫾ 0.4
1.1 ⫾ 0.1
Values are means ⫾ SE. Dorsal, dorsal flexion; plantar, plantar flexion; MVC, maximum voluntary contraction; TorqueMVC and ForceMVC, output torque and
force at MVC, respectively; Torquedeveloped and Forcedeveloped, output torque and force at 25% MVC, respectively; VASpain, visual analog pain scale; HR, heart
rate; MAP, mean arterial blood pressure; SV, stroke volume; CO, cardiac output; TPR, total peripheral resistance. *Significantly different from plantar.
†Significantly different from involuntary exercise.
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Fig. 3. Representative recordings of HR, arterial blood pressure (AP), and output torque in the time course during voluntary (left) and electrically evoked
involuntary (right) exercise of the ankle dorsal (top) and plantar (bottom) flexion. Note that, during voluntary exercise of dorsal flexion, the HR and AP increased
rapidly at the onset of the movement, and the increments lasted throughout the 2-min exercise.
CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
than that with dorsal flexion, as mentioned above. In the
involuntary condition, on the other hand, HR and AP were
unchanged with both dorsal and plantar flexion.
The time courses of the average cardiovascular responses
and the output force during static exercise are shown in Fig. 4.
There were no significant differences in the baseline values
between the protocols (Table 1). In the voluntary condition
(Fig. 4, left), a significant difference in the responses of HR,
MAP, and CO between the dorsal and plantar flexion was
detected, whereas the responses of SV and TPR were similar
between them. Compared with the baseline level, HR signifi-
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cantly increased at 20 –130 s from the force onset of voluntary
dorsal flexion; MAP significantly increased at 0 –120 s except
10 s; and CO significantly increased at 20 –130 s. On the other
hand, a significant change in MAP was detected only at the
onset of voluntary plantar flexion. In the involuntary condition,
there were no significant differences in the responses of HR,
MAP, SV, CO, and TPR between the dorsal and plantar flexion
(Fig. 4, right). Neither voluntary nor involuntary exercise
showed any difference in the relative output force between
dorsal and plantar flexion. In summary, in the voluntary condition, the increases in HR, MAP, and CO with dorsal flexion
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Fig. 4. The average changes (⌬; n ⫽ 10) in
HR, ⌬MAP, stroke volume (⌬SV), cardiac
output (⌬CO), and total peripheral resistance
(⌬TPR) from the baseline during voluntary
(left) and electrically evoked involuntary
(right) exercise of dorsal () and plantar
(ocirc) flexion in the time course. The average data of output force (%MVC) is also
shown in the bottom. Each value was calculated sequentially as the average over 10 s
immediately before each time point. The zero
in the time course refers to the moment that
the targeted force of 25% MVC was reached.
MU, medical unit (mmHg·ml⫺1·s⫺1). *Significantly different from the baseline (P ⬍
0.05). †Significantly different between dorsal
and plantar flexion (P ⬍ 0.05).
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
were greater than those with plantar flexion, while, in the
involuntary condition, there were no significant differences in
all parameters between dorsal and plantar flexion.
The cardiovascular responses before the onset of exercise.
To further examine the effect of central command on the
cardiovascular responses, HR and MAP immediately before
and after the force onset (motor threshold) were assessed (Fig. 5). In
the voluntary condition (Fig. 5, left), HR significantly increased from the baseline with dorsal flexion, but not with
plantar flexion, while MAP significantly increased from the
baseline with both dorsal and plantar flexion. HR significantly
increased 3 s before the force onset with dorsal flexion, and
MAP significantly increased 2–3 s before the force onset with
dorsal and plantar flexion. On the other hand, in the involuntary
condition (Fig. 5, right), no significant changes in HR and
MAP were observed compared with the baseline values, irre-
spective of dorsal or plantar flexion. A trend for an increase in
HR or MAP appeared after applying the stimulation (start cue)
and reached a peak around the time point at which the subjects
orally reported that they could feel the stimulation (sensory
threshold). However, there were no significant changes in HR
and MAP immediately before and after the force onset, suggesting that the electrically evoked muscle contraction had no
significant effects on the cardiovascular responses.
The correlation of the cardiovascular responses with Borg
scale or VASpain score. The maximum changes of HR
(⌬HRmax) and MAP (⌬MAPmax) against the Borg scale score
and VASpain score during voluntary and involuntary exercise
were assessed, respectively (Fig. 6). There was a significant
positive correlation between the Borg scale score and ⌬HRmax
or ⌬MAPmax during voluntary exercise, but not during involuntary exercise. Namely, the harder the subjects felt during
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Fig. 5. The average (n ⫽ 10) ⌬HR, ⌬MAP,
and output torque from the baseline before
and after the force onset of voluntary (left) and
electrically evoked involuntary (right) exercise of dorsal () and plantar (Œ) flexion. Each
value was calculated sequentially as the average over 1 s immediately before each time
point. The zero in the time point refers to the
force onset. The solid arrows below the time
scale refer to the events during dorsal flexion,
and the open arrows refer to the events during
plantar flexion. *Significantly different from
the baseline (P ⬍ 0.05).
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
677
voluntary exercise, the greater the HR and MAP increased. The
results suggested that the subjective index of the Borg scale
score mainly reflected the central effort rather than the effect of
the peripheral reflex. Instead, the VASpain score during involuntary exercise correlated positively with ⌬HRmax and
⌬MAPmax, indicating that the increases in HR and MAP during
involuntary exercise might be mainly attributed to the cutaneous reflex rather than the muscle reflex.
DISCUSSION
We have examined, using healthy human subjects, the question of whether central command produced differential contribution to the cardiovascular responses during voluntary static
exercise engaged by different muscle groups. The main findings of the present study are that, 1) during 2-min voluntary
exercise, there was a significant difference in the increments of
HR, MAP, and CO between the dorsal and plantar flexion,
while no difference in the responses of the SV and TPR
between them was obtained; 2) before voluntary exercise, HR
significantly increased with dorsal flexion alone, while MAP
increased with both the dorsal and plantar flexion; and 3) on the
other hand, electrically evoked involuntary exercise caused no
significant cardiovascular changes, irrespective of the dorsal or
plantar flexion. Taken together, it is suggested that the differential contribution of central command, rather than the peripheral reflex, is responsible for the different cardiovascular responses, depending on the strength of the central control.
J Appl Physiol • VOL
Involuntary exercise evoked by different modes of electrical
stimulation. By matching the same force level of the involuntary electrically evoked exercise to the voluntary one, the
muscle receptors would be stimulated at the same level, while
central command would be removed in the involuntary condition. The previous results, comparing the cardiovascular
responses between voluntary and involuntary exercise, contradicted each other; some studies showed the smaller cardiovascular responses to involuntary exercise than those to voluntary
exercise (13, 14), but another study did not (7). An important
candidate responsible for the discrepancy is involvement of
stimulating cutaneous receptors, because the conventional
transcutaneous EMS always activates not only the muscle, but
also the cutaneous receptors, including the pain receptors. In
the present study, therefore, we utilized a different mode of
electrical stimulation (LFS) for evoking involuntary exercise to
explore the sole effect of a muscle reflex. The present results
have shown that LFS was able to significantly reduce the
stimulating intensities for the sensory and motor threshold and
for generating a force (25% MVC) compared with the conventional EMS (Fig. 2). Furthermore, although the output force
was similar between the two modes of stimulation, the increases in HR and MAP were significantly less with the LFS
than those with the conventional EMS (Fig. 2). Thus, using
LFS with a lower current intensity, the effect of the cutaneous
reflex on the cardiovascular response to involuntary static
exercise was smaller than that in the case of the EMS used in
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Fig. 6. Relationships between the Borg scale score and the maximum ⌬HR (⌬HRmax) and ⌬MAP (⌬MAPmax) during voluntary (left) and electrically evoked
involuntary (middle) exercise (n ⫽ 10). Also shown is the relationship between the visual analog scale pain (VASpain) score and the ⌬HRmax and ⌬MAPmax during
involuntary exercise (right). The data of dorsal () and plantar (Œ) flexion were pooled. r, correlation coefficient. *P ⬍ 0.05. **P ⬍ 0.01.
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CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
J Appl Physiol • VOL
cutaneous receptors, including the pain receptors, rather than
that of the muscle receptors.
It is likely that, in the conscious condition, the muscle
mechanosensitive and metabosensitive reflexes play no dominant role in mediating the cardiovascular responses during a
relatively low-intensity exercise. Regarding the muscle mechanosensitive reflex, our laboratory has reported, using conscious
cats, that passive stretch of a limb evokes slight cardiovascular
responses, which are augmented by anesthesia (23, 25), and
that gadolinium, an inhibitor of stretch-induced ion channels,
does not alter the cardiovascular responses during voluntary
static exercise (24). In humans, passive ankle stretch produced
a limited increase in HR (17, 31), which could be enhanced by
sleep (21). These findings suggest that the muscle mechanosensitive reflex is suppressed in the conscious condition. On
the other hand, regarding the muscle metabosensitive reflex,
the present findings were in line with the previous data (15)
showing that the contribution of the muscle metabosensitive
reflex to the cardiovascular responses was small at a low to
moderate intensity (29 – 46% MVC) of voluntary static exercise. Nevertheless, Tokizawa et al. (37), using postexercise
ischemia, suggested a role of the metabosensitive reflex in
mediating the differential pressor response at the end of 2-min
voluntary static exercise. However, to our knowledge, it is well
known that HR returned promptly to the baseline during
postexercise ischemia (7, 10, 13, 14, 20), suggesting an insignificant role of the muscle metabosensitive reflex in control of
HR. The increases in HR and CO during voluntary static
exercise in this study, which mainly determined the rise in
MAP, could not be explained by the metabosensitive reflex.
Thus it is suggested that the central effects on the cardiac
pumping function, rather than the effects of muscle mechanosensitive and metabosensitive reflex, are responsible for the
differential cardiovascular responses during voluntary exercise
in the present study.
The neural mechanisms for differential cardiovascular responses to voluntary exercise. In the motor system, there is a
difference in the density of corticomotoneuronal connections,
depending on the limb muscles (2, 4 – 6, 8, 32, 38). The amount
of the monosynaptic connections between pyramidal tract neurons and spinal motoneurons determines the strength of direct
control by the motor cortex, which, in turn, characterizes the
function of the motoneurons and the muscles innervated. Compared with the flexor muscles of the lower limbs, the extensor
muscles that are thought to be the postural antigravity muscles
present relatively less corticomotoneuronal connections (2, 5,
6, 38), and, consequently, they may be activated predominantly
by a definite amount of neural circuits at the subcortical level.
In that case, the neural activities at the cortical level may be
relatively lower, and namely the smaller and weaker control by
central command is conceivable.
In the cardiovascular system, as shown in the present study,
the muscle-dependent cardiovascular responses seemed to be
similar to those in the motor system, suggesting the parallel
activation of the motor and autonomic circuits by central
command in the central nervous system (16). That is, the
stronger the cortical control of the exercise is, the larger the
increases in HR, CO, and AP are. The signal descending from
the cerebral cortex may simultaneously be given to the pontomedullary motor and vasomotor centers within the brain
stem. With voluntary dorsal flexion, a relatively stronger and
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the previous studies. Consequently, the exercise pressor reflex
arising from the stimulation of muscle mechanoreceptors and
metaboreceptors can be assessed more precisely in the present
study.
Effect of central command on the cardiovascular responses.
Although the previous studies have emphasized an importance
of the effects of muscle mechano- and metabosensitive afferent
activity on the cardiovascular responses during voluntary exercise, the dissimilar cardiovascular responses between different directions of movement in an identical leg in this study
cannot be fully explained by a difference in force development,
muscle mass, and/or fiber composition. Concretely, although
the absolute output force was lower during dorsal flexion,
almost one-half that of plantar flexion (Table 1), the increases
in HR, MAP, and CO during voluntary dorsal flexion were
obviously larger than those during voluntary plantar flexion.
During electrically evoked involuntary exercise, on the other
hand, all cardiovascular variables did not change significantly
from the baseline levels throughout either ankle flexion (Fig.
4). It is likely that a central mechanism, rather than the
peripheral muscle reflex, is responsible for the differential
cardiovascular responses to voluntary static exercise. The cardiovascular data before the force onset were in line with this
idea (Fig. 5). Since the muscle was relaxed at the moment, the
effects of the muscle reflex could be excluded completely.
Taken together, it is suggested that the cardiovascular responses before and at the beginning of static exercise are
mainly caused by central command. Since MAP elevates
according to increasing HR and CO during static exercise, the
obvious difference in the increments of HR, CO, and MAP, but
not in the SV and TPR, between voluntary dorsal and plantar
flexion suggested a difference in the effects of central command on the cardiac pumping function. Namely, the centrally
induced differential responses of sympathetic and parasympathetic outflow to the heart, rather than sympathetic outflows to
the peripheral vascular beds (e.g., muscle sympathetic nerve
activity), would contribute to the differential cardiovascular
responses during voluntary dorsal and plantar flexion in the
present study.
A role of the exercise pressor reflex in the cardiovascular
responses during voluntary exercise. There is evidence from
the animal studies that muscle afferent activities originating
from the contracting muscle may increase sympathetic discharges to the heart, kidneys, and adrenal glands (26, 27, 39,
40). In humans, it is suggested that stimulation of muscle
mechanoreceptors and metaboreceptors during static exercise
reflexly increases muscle sympathetic nerve activity (18, 20,
34). The differential cardiovascular responses to voluntary
exercise have been thought to be attributed to different effects
of the exercise pressor reflex, which are dependent on the force
development, muscle mass, muscle fiber composition, and
training state (11, 12, 28 –30, 37, 42). According to the present
results, however, the lack of the significant changes in HR and
MAP during electrically evoked involuntary exercise suggests
that the peripheral muscle reflex components do not play a
predominant role in mediating the cardiovascular responses.
The correlation analysis in Fig. 6 further revealed that the
cardiovascular responses in the voluntary condition were dependent on the exertion that the subjects perceived (the Borg
scale score), whereas those in the involuntary condition were
dependent on the VASpain score in relation to stimulation of the
CENTRAL CONTRIBUTION TO THE CARDIOVASCULAR RESPONSES
J Appl Physiol • VOL
pathetic nerve activities. The measurement of muscle sympathetic nerve activity could explore whether the metabosensitive
reflex has equivalent effects on the cardiovascular responses.
On the other hand, the measurement of cardiac sympathetic
and parasympathetic nerve activities would provide strong
evidence supporting our findings, although it is technically
difficult in humans.
Significance. We have shown that a central mechanism is
crucial for controlling the differential cardiovascular responses, depending on a muscular type of exercise. The extents
of the tachycardia and pressor responses were clearly different
between ankle dorsal and plantar flexion exercise in an identical lower limb, suggesting that the cardiovascular responses
varied, depending on the strength of the signals that the
muscles received from the supraspinal motor center. This
finding is important for us to avoid an unnecessary pressor
response during exercise in our daily living. Especially, in
patients with cardiovascular disease, e.g., heart failure and
hypertension, we may intend not to induce an undue stress on
the heart and a risky elevation of blood pressure by selecting
exercise, taking the differential contribution of central command into consideration.
Conclusion. Central command, rather than a peripheral muscle reflex, contributes predominantly to the cardiovascular
responses to voluntary static exercise with a relatively lower
intensity. Differential central command is reserved for different cardiovascular responses, depending on the strength of
central control of the muscles engaged during exercise.
GRANTS
This study was supported by a Grant-in-Aid for Scientific Research (B)
from the Japan Society for the Promotion of Science and was partly supported
by the Magnetic Health Science Foundation.
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
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