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1 School of Physical and Health Education and Department of Physiology, Queen's University, Kingston, Ontario K7L 3N6; and 2 Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The purpose of this study was to
test the hypothesis that sympathetic vasoconstriction is rapidly
blunted at the onset of forearm exercise. Nine healthy subjects
performed 5 min of moderate dynamic forearm handgrip exercise during
60 mmHg lower body negative pressure (LBNP) vs. without
(control). Beat-by-beat forearm blood flow (Doppler
ultrasound), arterial blood pressure (finger photoplethysmograph), and
heart rate were collected. LBNP elevated resting heart rate by ~45%.
Mean arterial blood pressure was not significantly changed (P = 0.196), but diastolic blood pressure was elevated
by ~10% and pulse pressure was reduced by ~20%. At rest, there
was a 30% reduction in forearm vascular conductance (FVC) during LBNP
(P = 0.004). The initial rapid increase in FVC with
exercise onset reached a plateau between 10 and 20 s of 126.6 ± 4.1 ml · min
1 · 100 mmHg1 in control vs. only 101.6 ± 4.1 ml · min1 · 100 mmHg1 in LBNP (main effect of condition,
P = 0.003). This difference was quickly abolished
during the second, slower phase of adaptation in forearm vascular tone
to steady state. These data are consistent with a rapid onset of
functional sympatholysis, in which local substances released with the
onset of muscle contractions impair sympathetic neural vasoconstrictor effectiveness.
muscle blood flow; Doppler ultrasound; lower body negative presssure
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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INCREASES IN SYMPATHETIC OUTFLOW are normally associated with constriction of arterioles in resting skeletal muscle (10, 11, 37, 38). However, both animal (22, 24, 25, 34) and human (7, 42) models provide evidence for a blunted responsiveness to sympathetic vasoconstriction in exercising muscle, referred to as functional sympatholysis (22).
It is not clear how soon after the onset of exercise sympatholytic mechanisms may begin to play a role. Earlier studies examining the adaptation of muscle blood flow to exercise have been obtained by using strain-gauge plethysmography to measure forearm blood flow (FBF) adaptation during sympathoexcitation (10, 31). However, this technique requires a pause of at least 5 s in exercise to measure blood flow, which prevents the assessment of the true dynamic response of blood flow during a rest-to-exercise transition. In fact, measurements of blood flow during intermittent pauses in exercise may more appropriately represent early postexercise responsiveness to sympathoexcitation.
Two recent studies have investigated the adaptation of blood flow during reflex sympathoexcitation by using Doppler ultrasound, which avoids the limitations of strain-gauge plethysmography. Shoemaker et al. (27) investigated the effect of posturally induced elevations in forearm sympathetic nervous activity on the early (up to 36 s) adaptation of FBF to exercise and found that blood flow was not initially compromised in upright vs. supine posture but that it was reduced by 36 s of exercise. In contrast, Tschakovsky and Hughson (39) assessed the FBF adaptation during sympathoexcitation evoked via ischemic calf exercise and demonstrated that, whereas resting forearm vascular conductance (FVC) was reduced during sympathoexcitation vs. control, it was normal within 20 s of the onset of exercise (39). However, blood pressure was elevated under these conditions, and it is unclear what role that may have played in the forearm vascular response.
The purpose of this study was therefore to test the hypothesis that
sympathetic vasoconstriction is rapidly overcome at the onset of
exercise under conditions where blood pressure is not elevated. We used
60 mmHg lower body negative pressure (LBNP) to evoke
baroreflex-mediated sympathoexcitation that has been demonstrated to
elevate forearm muscle sympathetic nervous activity (MSNA)
(32) without altering mean arterial blood pressure (MAP), and we measured the adaptation of hemodynamics to forearm exercise during control and LBNP conditions. The results are consistent with an
early onset and maintenance of functional sympatholysis during the
adaptation to exercise.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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General Methods
Subjects.
Nine healthy subjects [8 men and 1 woman; age 24.7 ± 0.7 (SE)
yr] participated in this study and gave written consent, on a form
approved by the Office of Human Research of the University of Waterloo,
after receiving full written and verbal details of the experimental
protocol and any potential risks involved. The subjects came to the
laboratory on one occasion before the experimental sessions for
assessment of their tolerance for 60 mmHg LBNP and to be familiarized
with the experimental protocol. Six additional subjects were tested in
this preliminary protocol but were excluded because of poor
tolerance of LBNP. Given the complexity of factors that can contribute
to orthostatic intolerance, it is not clear at this time whether this
subgroup would have demonstrated different forearm sympathetic
responses to exercise from the subjects that were able to complete the
study (5, 6). Furthermore, the efficacy of sympatholytic
mechanisms in orthostatic tolerant vs. intolerant subjects is currently unknown.
Subject monitoring. Subjects arrived at the laboratory in a rested state at least 2 h after eating. They assumed a supine position with their right arm extended to the side with the hand ~15 cm below heart level, and they were sealed from the level of the suprailiac crests in an LBNP box. Heart rate (HR) was monitored with an electrocardiogram standard CM5 lead placement. MAP was measured at heart level by using a photoplethysmograph finger blood pressure cuff (Ohmeda 2300, Finapres, Lakewood, CO) on the middle finger of the left hand.
FBF. Brachial artery mean blood velocity (MBV) was measured with a 4-MHz pulsed Doppler probe (model 500V, Multigon Industries, Mt. Vernon, NY) securely fixed to the skin over the brachial artery above the anticubital fossa (40). With this placement and arm position, probe insonation angle relative to the skin is 45° and the brachial artery is approximately parallel to the skin surface. Arterial cross-sectional area was measured by a separate, linear 7.5-MHz echo Doppler ultrasound probe operating in B mode (model SSH-140A, Toshiba, Tochigi-Ken, Japan) simultaneously with pulsed Doppler measures of brachial artery MBV during the second or third trial in each condition. This probe was positioned ~3 cm proximal to the pulsed Doppler probe to avoid acoustic interference between the probes. It has been shown previously in our laboratory that brachial artery diameters are not different between the two measurement sites (29). Beat-by-beat FBF was then derived as the product of brachial artery MBV and arterial cross-sectional area.
Forearm exercise. Exercise with the forearm consisted of smoothly raising and lowering an 8-kg weight through a vertical distance of 3.5 cm over a 1-s period in time with a signal light that set a work-rest duty cycle of 1 s-2 s. Within each work period, ~0.5 s was required for each of lifting and lowering the weight. With this exercise protocol, the average increase in FBF from rest was approximately sixfold. In our laboratory, this work rate typically results in small elevations in forearm venous blood lactate from 1 mmol/l at rest to 1.5 mmol/l in the first few minutes of exercise.
Elevation of systemic sympathetic nervous activity.
We evoked a reflex systemic sympathoexcitation by the application of
60 mmHg of LBNP. LBNP has been used extensively as a manipulation of
forearm MSNA (7, 11, 28, 31, 32, 44), and efficacy of
blockade of forearm MSNA is commonly confirmed by the observation of an
abolished forearm vasoconstriction during LBNP (21). LBNP
of 60 mmHg can be expected to evoke sustained, greater than twofold
increases in forearm MSNA (32).
Specific Experimental Protocol
We investigated the effect of60 mmHg LBNP-induced reflex
sympathoexcitation on the adaptation of systemic (HR, blood pressure) and forearm hemodynamics (FBF, FVC) during a transition from rest to
dynamic forearm handgrip exercise by comparing the responses during
control (no LBNP) and systemic sympathoexcitation (60 mmHg LBNP). The
order of the experimental conditions was counterbalanced among subjects
with each subject acting as his or her own control. All experimental
conditions were conducted during one session in the laboratory.
In each experimental condition, subjects performed at least two trials
with a rest period of at least 10 min between exercise to allow for
return of FBF to baseline values. Doppler measures of brachial artery
MBV were observed to be sure that a stable baseline was present, and
then data were collected for 1 min at rest followed by 5 min of forearm
exercise. During the LBNP condition, 60 mmHg LBNP began 4-5 min
before the start of exercise to achieve a stable hemodynamic baseline
and was terminated immediately at the end of exercise. Pilot work had
indicated that it was difficult for subjects to withstand >9 min of
LBNP without exhibiting signs of presyncope. To eliminate the
effects of anticipation, subjects remained unaware of the time in any
trial and were simply told at the appropriate time to begin or to cease exercise.
Because we were interested specifically in FBF changes, we reduced skin and hand blood flow in the subjects by cooling the arm over a period of 30-40 min with the aid of a fan. In some cases, subjects held a bottle of ice water (39) for 10-15 min to accelerate the cooling, but this bottle was removed well before the onset of the exercise trials. Once brachial artery MBV (pulsed Doppler) monitored during this period was observed to stabilize at minimal levels characterized by systolic pulse flow only and little flow variability, forearm cooling was maintained with a fan. Room temperature was between 21 and 23°C during testing.
Data acquisition and analysis.
Imaged data were saved on videotape for subsequent analysis. Arterial
diameter was measured four times at rest; at 5, 10, 20, and 30 s;
and thereafter every 30 s during forearm exercise. Diameter
measurements at these times consisted of the average of three separate
caliper measures of a frozen screen image of the brachial artery during
diastole. All measurements were performed by the same operator. For
each subject, the diameter data were fit with an exponential regression
to reduce random measurement error and provide continuous diameter
estimates to match with the beat-by-beat MBV to allow calculation of
FBF. The use of an exponential function to fit the brachial artery
diameter responses to forearm exercise is consistent with the time
course profile of diameter responses observed previously in our
laboratory (26). The electrocardiogram, arterial blood
pressure, and brachial artery MBV signals were digitized at 100 Hz and
stored on a computer. The data were analyzed off-line, with the
beat-by-beat data averaged into 3-s bins corresponding to the
contraction-relaxation duty cycle, and then averaged across all subject
trials to determine the mean response profile. FBF was
calculated as
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Statistical Analysis
The effects of condition (LBNP vs. control) and time (rest vs. exercise) on central hemodynamic variables (HR and arterial blood pressure) was assessed with two-way repeated-measures ANOVA. For FBF and FVC, specific hypothesis testing (effect of condition at rest, effect of LBNP on the magnitude of the initial rapid increase in blood flow, effect of LBNP on the secondary slower increase in blood flow, effect of LBNP on the steady-state exercise response) was performed with one-way repeated-measures ANOVA at rest, and two-way repeated-measures ANOVA for each of the initial rapid increase in blood flow (phase I; first 20 s of exercise), the secondary slower increase in blood flow (phase II; 30-150 s of exercise), and the steady state (phase III; 180-300 s of exercise). Post hoc analysis was performed by using Tukey's test for pairwise comparisons. Significance was set at P < 0.05. Data are presented as means ± SE. All tests were completed with a commercial statistical package (SigmaStat 2.03, SPSS).| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Systemic Cardiovascular Responses
HR (see Fig. 1A).
There was a main effect of LBNP on HR (P = 0.001).
Resting HR was increased by ~45% compared with control during 60
mmHg LBNP (86.1 ± 3.7 vs. 59.2 ± 4.2 beats/min;
P < 0.0001). Over the course of the 5 min of handgrip
exercise, HR remained higher in the LBNP tests. In addition, there was
a significant increase in HR above resting values by 20 s of
exercise for control (P = 0.001) and by 90 s of
exercise for 60 mmHg LBNP (P = 0.001).
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Arterial blood pressure (see Fig. 1B). There was an interaction between condition and time for systolic blood pressure (SBP; P < 0.001) such that SBP was not significantly different between control and LBNP until 120 s of exercise (Fig. 1B). In addition, SBP gradually increased above resting values in the control condition such that by 120 s of exercise it was significantly greater (P = 0.008) than rest, whereas SBP did not change with forearm exercise in LBNP.
There was also an interaction between condition and time for diastolic blood pressure (DBP; P < 0.001). However, in contrast to SBP, DBP was significantly elevated at rest in the LBNP condition vs. control (84.6 ± 2.5 vs. 77.2 ± 2.0 mmHg; P = 0.018), but a progressive increase in DBP during forearm exercise in the control condition caused the difference between LBNP and control to disappear by 150 s of exercise. There was an interaction between condition and time for MAP (P < 0.001) such that, although MAP was not statistically different between control and LBNP at any time point and did not change over time in LBNP, MAP increased progressively in control and was significantly elevated compared with rest by 90 s of exercise (P = 0.049).Forearm Vascular Responses
Brachial artery diameter. There was an interaction between condition and time for brachial artery diameter (P < 0.001). No difference in brachial artery diameter was observed between LBNP and control at rest (4.3 ± 0.1 vs. 4.3 ± 0.1 cm). However, brachial artery diameter was slightly but significantly elevated in LBNP vs. control at 10, 30, and 40 s of exercise. Furthermore, brachial artery diameter was significantly elevated above rest at 40 s, at 90 s, and from 210 to 300 s of forearm exercise in LBNP, and from 210 to 300 s of exercise in control.
FBF (see Fig. 2A).
There was no effect of LBNP on FBF at rest (control: 34.1 ± 5.5 ml/min vs. LBNP: 33.5 ± 5.1 ml/min; 1-way ANOVA,
P = 0.871). With the onset of exercise, FBF increased
rapidly in a biphasic manner in both conditions. There was a main
effect of condition for FBF (P = 0.004) during the
initial rapid increase in FBF, such that in LBNP FBF only increased to
99.1 ± 3.5 vs. 119.0 ± 3.5 ml/min for control. This
attenuated phase I increase in FBF during the LBNP tests was
quickly overcome during the phase II adaptation such that
FBF was not different (main effect for condition, P = 0.163). However, a significant difference between LBNP and control was
evident during the steady state (LBNP: 185.7 ± 2.7 ml/min vs.
control: 200.1 ± 2.7 ml/min; main effect for condition, P = 0.005).
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FVC (see Figs. 2B, 3, and 4).
Calculation of FVC as FBF/MAP
indicated no difference in forearm vessel
tone at rest during LBNP vs. control (34.9 ± 6.2 vs. 36.3 ± 6.6 ml · min1 · 100 mmHg1; main effect for condition, P = 0.570; Fig. 2B). However, although the characteristics of
the forearm arterial inflow pulse per cardiac cycle varied somewhat
from subject to subject, a closer examination revealed characteristics
consistent with a downstream vasoconstriction in the forearm (Fig. 3),
whereby peak systolic velocity was attenuated in LBNP and there was a
greater retrograde flow velocity pulse (2). Thus the net
pulse of blood entering the forearm per cardiac cycle was diminished
despite similar SBP and elevated MAP. Further examination of the
characteristics of arterial inflow during a cardiac cycle demonstrated
a period of zero inflow during diastole, despite significant arterial
driving pressure. Taken together, these observations indicated to us
that the use of MAP to assess forearm resistance vessel tone during
conditions where there is zero diastolic inflow may be inappropriate.
Given this apparent "uncoupling" of arterial pressure and arterial
inflow during diastole, which may reflect a vascular waterfall in
vasoconstricted tissue (17), we sought to evaluate
arterial resistance vessel tone by excluding the period of zero
diastolic arterial inflow. Because arterial inflow occurred
only during systole, we calculated FVC as arterial inflow per cardiac
cycle divided by SBP (see Fig. 4). This analysis unmasked an ~30%
forearm vasoconstriction at rest during LBNP vs. control (0.46 ± 0.09 vs. 0.326 ± 0.07 ml · cardiac
cycle1 · mmHg SBP1;
Fig. 4).
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1 · 100 mmHg1 in control vs. only 101.6 ± 4.1 ml · min1 · 100 mmHg1 in LBNP (main effect of condition,
P = 0.003). Thereafter, FVC was not different between
control and LBNP during phase II (main effect of condition,
P = 0.08) or during steady state (main effect of
condition, P = 0.225).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Although it has been clearly established that the responsiveness of an exercising muscle vascular bed to increased sympathetic neural vasoconstriction in steady-state exercise is blunted in animal (25, 34) and human (7, 42) models, it is unknown how rapidly such blunting occurs in a rest-to-exercise transition. Given the potential impact of exercising muscle blood flow and vascular conductance adaptation on muscle metabolic and blood pressure adaptation to exercise (9, 20, 36), understanding how opposing sympathetic neural and local vasoregulatory factors interact to determine muscle vascular bed adaptation is of considerable importance.
This study tested the hypothesis that sympathetic vasoconstriction is
rapidly overcome at the onset of exercise in human muscle under
conditions in which blood pressure is not elevated. The major novel
findings of this study are 1) reflex sympathoexcitation blunts the rapid (0-20 s of exercise), phase
I adaptation of FBF to exercise, and 2) this
impairment is abolished within the first 10 s of the phase
II blood flow adaptation and remains abolished throughout 5 min of
exercise. These new data provide evidence that local vasodilatory
mechanisms associated with phase II of the blood flow
adaptation to exercise can rapidly compensate for the initial blunting
of flow during 60 mmHg LBNP-induced reflex sympathoexcitation and
restore the normal blood flow adaptation to exercise. Thus they provide
an important contribution to the debate concerning the efficacy of
functional sympatholysis.
Systemic Hemodynamics During Reflex Sympathoexcitation
Elevations in HR and DBP observed in this study are consistent with previous reports supporting an autonomic nervous system-mediated effort to maintain blood pressure in the face of a translocation of blood volume from the central circulation to the lower limbs during LBNP (18, 19). The slight (2-3 mmHg) increase in SBP, DBP, and MAP by 1.5 min of forearm exercise in the control condition but not during LBNP suggests that this level of forearm exercise may have evoked a slight increase in systemic sympathetic nervous activity. However, such an increase either did not occur against a background of already elevated sympathetic nervous activity in LBNP or, conversely, if it did occur, was not able to significantly affect these variables. In contrast, a rapid but modest increase in HR was evident at the onset of forearm exercise in both control and LBNP. It is possible that this indicates a central command-mediated parasympathetic withdrawal (16). However, this study was not designed to detect the specific nature of the mechanisms regulating cardiac responses to forearm exercise.Assessing Resting Forearm Vascular Tone During Reflex Sympathoexcitation
LBNP of60 mmHg activates reflexes arising in cardiopulmonary
and carotid baroreceptors and elevates sympathetic nervous activity.
The net effect is an elevation in HR and peripheral vasoconstriction in
an effort to maintain blood pressure (1). Increases in
forearm MSNA with 60 mmHg are roughly twofold (32).
Some investigators have observed reductions in FBF with LBNP, indicating increased forearm vascular resistance (10, 31, 37, 38). Although we did not observe a reduction in FBF per minute during LBNP at rest in this study, nor a reduction in FVC calculated as FBF/MAP, we did observe key differences in brachial artery blood flow per beat that were consistent with forearm vasoconstriction. When skin blood flow is minimized, brachial artery inflow to the resting forearm occurs only during systole (Fig. 3) despite the fact that there is considerable DBP. This is a key consideration when evaluating the pressure-flow relationship in the forearm. Because SBP was not different between LBNP and control and DBP was actually elevated, we would expect that the volume of blood entering the forearm per heartbeat would be the same in LBNP vs. control if downstream conductance was the same. Instead, it was substantially reduced in LBNP and was characterized by a lower peak systolic velocity and/or a greater retrograde velocity (Fig. 3). This is entirely consistent with downstream vasoconstriction (2), and indeed assessment of forearm vascular tone as the volume of blood entering the arm during systole divided by SBP (Fig. 4) revealed such a vasoconstriction. The fact that total FBF per minute was not different can be attributed to the ~45% elevation in HR with LBNP. This likely compensated for the reduced blood flow per beat at the same arterial blood pressure by increasing the number of albeit smaller systolic "pulses" of blood entered the forearm per minute and reducing the time of zero arterial inflow per beat.
These observations are also consistent with the recent findings of Shoemaker et al. (27), who did not observe a reduction in resting FBF in upright vs. supine posture. However, these authors did not elaborate on the potential effects of HR in masking vasoconstriction in the resting forearm and the need to account for the uncoupling of DBP and arterial inflow evidenced by zero forearm arterial inflow during diastole.
Adaptation of FBF to Exercise During Reflex Sympathoexcitation
With the onset of exercise, blood flow occurs throughout the cardiac cycle, such that any changes in vascular resistance should be evident from measures of FBF and MAP. We observed a characteristic biphasic adaptation of FBF, consistent with previous observations from our laboratory (20, 30, 39). In the initial phase of adaptation to exercise, both FBF and FVC quickly reached stable values that were 17 and 20% less in LBNP vs. control, respectively. This suggests that elevated forearm MSNA can restrain dilation of the forearm muscle vascular bed during the first 20 s of exercise, and it is consistent with observations of DeLorey et al. (4), who observed reductions in the percent increase in FBF after a single contraction in LBNP vs. control.In contrast, Shoemaker et al. (27) have demonstrated a reduced FBF after a single contraction in upright vs. supine posture that was unrelated to differences in sympathetic tone but sensitive to postural adjustments in venous volume and pressure. LBNP and upright posture are known to reduce central venous pressure (23), which can lead to reduced forearm venous pressure and volume (27). Because the forearm was in a slightly dependent position in our study, it is possible that LBNP evoked a reduction in forearm volume vs. control at rest, reducing the effect of the muscle pump contribution to the initial adaptation of FBF (41). Whether this can explain all, some, or none of the difference in the magnitude of the phase I adjustment in FBF cannot be confirmed because the necessary measurements of microvenule pressure are not possible. However, given the clear vasoconstriction present at rest, it seems likely that sympathetic vasoconstriction is a contributing factor to the early deficit in blood flow adaptation during LBNP.
The LBNP-induced restraint of FBF and FVC that was apparent in phase I was quickly abolished during the second (phase II), slower adjustment of FBF to steady state (Fig. 2, A and B). Because further increases in MAP would not occur as exercise continued, this observation is consistent with vasodilation in LBNP increasing to match that during control in phase II. This is entirely consistent with our previous findings where reflex sympathoexcitation was evoked via ischemic calf exercise (39). However, in that study we could not be sure that differences in blood pressure between control and reflex sympathoexcitation did not confound the results. The present study provides further support for an early onset and maintenance of functional sympatholysis during the adaptation to exercise in human forearm muscle.
Sites and Mechanisms of Early Functional Sympatholysis
The mechanisms responsible for the time-dependent pattern of FBF and FVC observed in this study in the face of increased reflex sympathoexcitation require consideration across the time scale of the experiments. In a previous experiment, we demonstrated that excess flow during the transition from rest to moderate forearm exercise was not attenuated until 5 min of exercise, indicating a relatively slow vasodilator washout effect on vascular conductance (39). Given how rapidly blood flow was normalized in LBNP, it is therefore unlikely that it was due to an additional accumulation of metabolites exerting a direct vasodilatory effect in LBNP. Instead, we interpret these data to be consistent with sympatholytic effects of substances released early in exercise antagonizing the additional sympathetic neural vasoconstriction in LBNP. Candidates mediating this effect would have to reach adequate biological activity by 30 s of exercise onset and might therefore include nitric oxide (35) and/or K+ (13). Endothelial response to increases in blood flow velocity is rapid (12), and experiments in animal (14, 15, 35) and human (3, 42) models have provided evidence for a sympatholytic effect of nitric oxide. Alternatively, interstitial K+ concentrations rise within a few seconds of the onset of contractions (8), and K+ has been demonstrated to inhibit norepinephrine release from adrenergic nerves (13).Limitations of the Experimental Model
Assessment of the interaction of elevated sympathetic neural influences and local vasodilator influences in the present study rests on the assumption that60 mmHg LBNP induced elevations in forearm
MSNA. In the present study, we were unable to measure MSNA or
norepinephrine kinetics in the forearm. However, it has been
demonstrated that levels of LBNP as used in this study evoke greater
than twofold elevations in sympathetic neural activity in the forearm
(32). In addition, we detected a 30%
vasoconstriction at rest during LBNP as measured just before the onset
of forearm exercise. Therefore, we are confident that a substantial
sympathetically mediated increase in forearm vessel tone was achieved
with LBNP.
An additional concern with regard to reflex sympathoexcitation is that
elevated levels of circulating epinephrine may have contributed to
counteracting the effect of local forearm sympathetic vasoconstriction.
Indeed, Reed et al. (21) demonstrated that an underlying
2-receptor-mediated vasodilatory mechanism was activated
during reflex sympathoexcitation via contralateral ischemic handgrip exercise to exhaustion. Evidence to date on whether
circulating epinephrine levels increase with LBNP is equivocal
(5, 43, 33). Even if they do, it is unlikely to explain
our results for the following reasons. First, we maintained LBNP for 5 min before the start of forearm exercise in an attempted to achieve a
"steady-state" autonomic nervous response before the onset of forearm exercise, yet there was substantial vasoconstriction at rest
immediately before the onset of exercise. Second, the early forearm
vascular response indicated a blunted vasodilation during LBNP.
Finally, the abolishment of the blunted vasodilation was too rapid to
be explained by changes in circulating epinephrine. Thus we believe
that the rapid restoration of a "normal" FVC in LBNP is consistent
with local factors blunting the effect of forearm sympathetic vasoconstriction.
Conclusions
In summary, this study is the first to clearly demonstrate the time course of functional sympatholysis in exercising human forearm muscle and thereby to provide insight into potential mechanisms. We have demonstrated that the magnitude of the initial phase of blood flow adaptation at the onset of exercise is attenuated. However, local factors rapidly (within 30 s of exercise onset) compensate for this initial blood flow deficit, providing evidence for an early onset of functional sympatholysis. It remains to be determined which mechanisms are involved in such a rapid blunting of sympathetic vasoconstriction.| |
ACKNOWLEDGEMENTS |
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The authors thank Dr. Gordon Stubley for valuable insight and criticism and Dave Northey, Heather Naylor, and Mike Chambers for excellent technical assistance.
This work was supported by the Natural Sciences and Engineering Research Council of Canada.
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FOOTNOTES |
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Address for reprint requests and other correspondence: M. E. Tschakovsky, School of Physical and Health Education, Queen's University, Kingston, ON, Canada K7L 3N6 (E-mail: mt29{at}post.queensu.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published January 10, 2003;10.1152/japplphysiol.00680.2002
Received 25 July 2002; accepted in final form 7 January 2003.
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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