Journal of Applied Physiology
Vol. 82, No. 4, pp. 1237-1243, April 1997
CONTROL OF BREATHING, CIRCULATION, AND TEMPERATURE

Sympathetic outflow to the skeletal muscle in humans increases during prolonged light exercise

Mitsuru Saito, Ryoko Sone, Masao Ikeda, and Tadaaki Mano

Laboratory of Applied Physiology, Toyota Technological Institute, Nagoya 468; and Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-01, Japan

ABSTRACT

INTRODUCTION

METHODS

RESULTS

DISCUSSION

ACKNOWLEDGEMENTS

FOOTNOTES

REFERENCES

ABSTRACT

Saito, Mitsuru, Ryoko Sone, Masao Ikeda, and Tadaaki Mano. Sympathetic outflow to the skeletal muscle in humans increases during prolonged light exercise. J. Appl. Physiol. 82(4): 1237 - 1243, 1997.To investigate the effects of exercise duration on muscle sympathetic nerve activity (MSNA), heart rate, blood pressure (BP), tympanic temperature, blood lactate concentration, and thigh electromyogram were measured in eight volunteers during 30 min of cycling in the sitting position at an intensity of 40% of maximal oxygen uptake. MSNA burst frequency increased 18 min after exercise was begun (25 ± 4 bursts/min at baseline and 36 ± 5 bursts/min at 21 min of exercise), reaching 41 ± 5 bursts/min at the end of exercise. Heart rate and systolic BP increased during exercise. Twenty minutes after commencement of exercise, however, both systolic and diastolic BP values tended to drop compared with the initial period of exercise. Tympanic temperature increased in a time-dependent manner, and the increment was significant 12 min after exercise was begun. Blood lactate concentration and integrated electromyogram showed no significant changes during exercise. The increased MSNA during prolonged light-intensity exercise may be a secondary effect of the drop in BP as a result of blood redistribution caused by thermoregulation rather than by metaboreflex.

blood pressure; blood redistribution; body temperature; autonomic response to exercise

INTRODUCTION

PROLONGED EXERCISE ELICITS marked hemodynamic changes, a time-dependent increase in heart rate, splanchnic vasoconstriction, skin vasodilatation, and a gradual reduction of arterial blood pressure (5, 10, 19). These cardiovascular alterations during prolonged exercise are mediated, at least in part, by the exercise-induced rise in body temperature (5, 19). The sympathetic nervous system may play an important role in regulating these exercise-induced cardiovascular alterations, e.g., for maintaining systemic blood pressure and cardiac output to meet metabolic demands and body temperature regulation.

Muscle sympathetic nerve activity (MSNA) during exercise is modulated reflexively by changes in both arterial blood and central venous pressures; i.e., decreased arterial blood and central venous pressures enhance MSNA (27, 29). Because body temperature rises are accompanied by decreased blood pressure and central venous pressure at rest as well as during exercise (10, 19), this suggests that prolonged exercise could enhance MSNA as a result of decreased blood pressure with exercise-induced hyperthermia.

The sympathetic outflow to the inactive skeletal muscle during exercise performed over relatively short periods does not increase if exercise intensity is below a critical level, i.e., 20% of maximal voluntary muscle contraction for static muscle contraction (31) or ~40% of maximal oxygen consumption (O_{2 max}) for dynamic muscle contraction (26).

However, recent studies of norepinephrine (NE) spillover as a marker of MSNA during dynamic exercise have demonstrated increased sympathetic nerve activity during low- to light-intensity (~39% of O_{2 max}) prolonged cycling (<15 min) (26, 31), suggesting that the sympathetic nerve response to dynamic exercise may be influenced by exercise duration even at low intensity. Furthermore, Batman et al. (1) reported significant increases in MSNA in subjects during prolonged rhythmic isotonic handgrip exercise while they were in the supine position, with no changes in contracting muscle acidosis throughout exercise. Ray (16), however, found no increase in MSNA in subjects during prolonged one-legged dynamic exercise at a power output of 30 W for 40 min while they were in the sitting position. The MSNA response to muscular exercise is affected by a number of factors, i.e., the exercise mode, intensity of exercise, duration, muscle mass, and position during exercise (13, 17, 22, 29, 37). Thus the exercise intensity and duration may be important factors determining the response in MSNA during exercise. We investigated whether MSNA increased during light-intensity prolonged leg exercise by using intraneural recording of sympathetic nerve activity. These results demonstrated that the MSNA increased during prolonged light-intensity dynamic exercise without significant elevation in blood lactate concentration. This suggests that exercise duration is one of the factors that modulates MSNA response to dynamic exercise, the mechanisms of which are discussed in this paper.

METHODS

Subjects

Measurements

Heart rate counted from electrocardiograms, systolic and diastolic blood pressures determined by finger arterial blood pressure (Finapres 2300, Ohmeda), tympanic membrane temperature (T_ty; model K210, Technol Seven, Tokyo, Japan), and surface electromyogram (EMG) activity of the vastus lateralis were measured continuously during the experiments. Mean blood pressure was calculated as one-third of pulse pressure plus diastolic pressure. Esophageal temperature was measured in two subjects. Blood samples were drawn from the finger tip at rest and at 2, 5, 10, 20, and 30 min of exercise, and blood lactate concentration was analyzed by an electrode-enzymatic method (1500 Sport, Yellow Springs Instruments, Yellow Springs, OH).

O_{2 max} was determined by a stepwise exercise protocol on an electrically braked ergometer (Aerobike 800, Combi, Tokyo, Japan) with the subjects in the sitting position. Step exercise was composed of three levels of load every 4 min, after which the load was increased by 15-20 W/min until volitional exhaustion. Expired gas was collected in a Douglas bag, and then oxygen and carbon dioxide contents were analyzed with an expired-gas monitor (model 1H2A, San-Ei, Tokyo, Japan).

Protocol

Table 1. Physical characteristics of subjects and exercise rate in the exercise study Men (n = 6) Women (n = 2) Age, yr 24 ± 1  25 ± 3  Height, cm 173 ± 1  162 ± 2  Body weight, kg 65 ± 3  51 ± 6   O2 max, l/min 2.26 ± 0.18  1.99 ± 0.27   O2 max per body wt, ml · kg1 · min1 49 ± 4  39 ± 1  Exercise rate, W 98 ± 6  69 ± 1 Values are means ± SE; n, no. of subjects. O2 max, maximal oxygen consumption.

Analysis and Statistics

RESULTS

Control Study

Exercise Study

Average baseline MSNA burst frequency was 25 ± 4 bursts/min. This value decreased by 24% (P < 0.05) during the first 3 min of exercise and then increased gradually, reaching a significant increase of 41% (36 ± 5 bursts/min; P < 0.05) at 19-21 min from the start of exercise. For the last 3 min of exercise, MSNA burst frequency reached 41 ± 5 bursts/min (160% of the baseline value).

Heart rate rose immediately after the onset of exercise, and the increase from the baseline value of 65 ± 4 to 101 ± 4 beats/min after the first 3 min of exercise was significant. Heart rate increased continuously to 113 ± 6 beats/min (11% or 12 beats/min) during the last 3 min of exercise.

Average baseline systolic and mean blood pressures were 125 ± 5 and 93 ± 4 mmHg, respectively. These values increased significantly to 140 ± 8 and 99 ± 5 mmHg, respectively, during the first 3 min of exercise and reached maximal levels of 146 ± 8 and 99 ± 6 mmHg, respectively, after 7-9 min of exercise. Thereafter, systolic and mean blood pressures tended to drop in a time-dependent manner during exercise, but systolic blood pressure remained above the baseline value. The systolic and mean blood pressures decreased by 6 and 6% (136 ± 7 and 93 ± 5 mmHg), respectively, at 19-21 min and by 7 and 6% (135 ± 5 and 93 ± 5 mmHg), respectively, during the last 3 min of exercise from the highest value at 9-11 min of exercise. These differences were significant. The average diastolic blood pressure was 77 ± 5 mmHg at baseline, and a tendency to decrease during the last half of the exercise period was observed (71 ± 5 mmHg for 16-18 min of exercise, 72 ± 3 mmHg for 22-24 min, and 70 ± 4 mmHg for 25-27 min of exercise; P < 0.05), whereas those during the first half of the exercise period were almost the same as the baseline values.

Blood lactate concentration showed no significant changes during exercise.

Baseline T_ty was 36.98 ± 0.07°C. This value increased continuously during exercise, reaching 37.13 ± 0.09°C after 12 min of exercise (P < 0.05) and 37.39 ± 0.05°C at the end of the exercise period.

There were no significant changes in integrated EMG during exercise.

DISCUSSION

The most important finding in this study was that MSNA increased during prolonged light-intensity dynamic exercise without elevation of blood lactate concentration. This increase was observed 19-21 min from the beginning of exercise and was accompanied by concomitant reductions in systolic and diastolic blood pressures. T_ty increased 12 min after commencement of exercise, preceding the increase in MSNA burst frequency and drop in blood pressure. In the control study, there were no changes in MSNA, T_ty, or cardiovascular parameters, indicating no effect of sitting position or time on MSNA response at rest.

No increases in MSNA were found previously during low- to moderate-intensity exercise for several minutes (26, 32, 37) or during prolonged one-leg dynamic exercise (16) at an intensity corresponding to a heart rate of >110 beats/min. In this study, MSNA did not increase during the initial 15 min of exercise at low-to-moderate intensity, in agreement with these previous studies. However, the significant increase in MSNA 18 min after the beginning of exercise seen here was in marked contrast to Ray's findings. This difference may have been due to factors such as exercise intensity (26), active muscle mass (28, 31), and exercise type (22). In Ray's study, power output was an average of 36 W with one-leg exercise performed by subjects with relatively small muscle mass in the sitting position.

The slight but significant decrease in MSNA burst frequency during the initial period of exercise observed here coincided with the results of previous studies (4, 17, 26). The mechanism of this decrease may involve the response to central and peripheral input to MSNA during sitting bicycle exercise. Because MSNA neurons receive strong inhibitory input from baroreceptors (38), increased arterial blood pressure and/or cardiopulmonary mechanoreceptor stimulation caused by enhanced venous return with dynamic muscle contraction (17, 23) could suppress muscle sympathetic outflow. Alternatively, inhibitory effects of central drive on MSNA response might be involved in this reduction in burst frequency, as suggested previously to occur during brief dynamic and static muscular exercise performed at low to moderate intensity (4, 14). The inhibition of the excitatory reflex effect on MSNA, e.g., metaboreflex, might be weak at the initial phase of light cycling exercise (see below).

Recently, Leuenberger et al. (13) reported a similar response in sympathetic activity; a significant increase was observed in sympathetic activity assessed by norepinephrine (NE) spillover during upright prolonged low-intensity cycling, although the exercise intensity at 20% of O_{2 max} (62 ± 3 W) used was lower than that in our study (averaged 98 W for men and 69 W for women). Furthermore, they found that NE spillover had increased at 10 min after the beginning of exercise (13, 28), earlier than in this study in which MSNA showed no elevation until 18 min after commencement of exercise. These differences in responses of sympathetic nerve activity to low-intensity exercise and during the initial period of exercise may have been due to methodological factors; we directly recorded sympathetic outflow to the forearm skeletal muscle, which is a relatively restricted site, whereas NE spillover in the leg or upper limb involves not only skeletal muscle but also other tissues such as the skin. Sympathetic outflow to these tissues varies during muscular exercise (24).

The MSNA enhancement during muscle contraction has been mainly considered to be due to afferent input from active skeletal muscle chemoreceptors, i.e., metaboreflex (14, 35). This reflex arc could be evoked predominantly by metabolic substrates produced by muscle contraction (31): lactic acid is used as an index of the metabolic condition. In this study, however, we found no elevation of blood lactate concentration throughout the period of exercise. Thus the metaboreflex would not have significantly affected the MSNA response during prolonged exercise, and other mechanisms must be considered to explain the rise in MSNA during prolonged light-intensity exercise.

Recent studies have shown that group III mechanosensitive afferent responses elicited by muscle contraction can involve cardiovascular reflexes (15, 36). Because these slow-conduction nerve group III responses are also modulated by thermal stimuli (9) and the metabolic by-product arachidonic acid (18), exercise-induced rises in temperature in active skeletal muscle and metabolic by-products may have altered group III muscle afferent activity during prolonged low-intensity dynamic exercise. However, we speculate that the mechanoreceptor reflex effect on increased MSNA in this study would be small relative to the baroreflex effect (see below). First, no increase in MSNA occurred in the initial phase of dynamic exercise when group III muscle afferent activity may increase. Second, in addition to the effects of skeletal muscle contraction per se, elevation in body temperature could cause marked hemodynamic alterations such as decreases in blood pressure and redistribution of blood volume.

On the other hand, Hayward et al. (8) demonstrated that group III muscle afferent activity was also sensitized after muscle fatigue in the cat. In this study, however, we did not detect muscle fatigue as we examined power output and EMG.

Kregel et al. (12) showed that nonexertional body heating elicits regional vasoconstriction in barodenervated rats. This suggests that the central and peripheral thermoreceptor reflexes may evoke sympathetic nerve activity directly. However, there was regional specificity in the sympathetic nerve response; i.e., potent responses were seen in internal organs but no significant responses were detected in skeletal muscle (11). Thus we determined T_ty as an index of central temperature, and an increase was detected 12 min after the start of exercise. Because T_ty is correlated with the brain temperature (3), this observation suggests that elevation of central temperature produced by internal body heating with dynamic exercise could directly affect the central sympathetic nervous system. Grewe et al. (6) recently reported, however, that muscle vasoconstrictor nerve activity was not elicited in cats by warming the subhypothalamic region while reduced activation of the cutaneous vasoconstrictor nerve was observed, suggesting little direct effect of elevation of brain temperature on MSNA outflow. Nevertheless, in the present study the possibility that peripheral thermal stimuli might modulate activities of group III as well as group IV muscle afferent nerves (9) and subsequent increases in MSNA could not be excluded.

MSNA is strongly modulated by both arterial and cardiopulmonary baroreceptors (38). When arterial blood pressure (29) as well as central venous pressure decrease (27) during exercise, MSNA increases. In addition, MSNA burst rate shows an inverse correlation with diastolic blood pressure at rest (38). Zinik et al. (39) reported decreased venotone and increased skin blood flow during dynamic exercise corresponding to the point at which T_ty increased. This indicates that blood would shift from the deep regions to the surface of the body because of vasodilatation in response to hyperthermia. This would decrease central blood volume and lower blood pressure (5, 19, 26). Although we did not measure skin blood flow or central venous pressure, significant reductions were observed in systolic and diastolic blood pressures concomitantly with a rise in T_ty during the last half of the exercise period compared with the value during the initial period of exercise. From these results, the increase in MSNA during prolonged light-intensity exercise could represent a secondary effect of the drop in blood pressure rather than a direct effect of body temperature elevation on central MSNA neurons. However, there was a time lag between the increase in T_ty and drop in blood pressure, which might be explained by deviation between T_ty and vasomotor responsiveness.

Muscle fatigue has been suggested to influence increases in MSNA during exercise (23, 30). Although there are limitations of using EMG as an index of central and/or peripheral fatigue in working muscles, no significant changes in integrated EMG were observed during exercise. Thus we suppose that central motor command and muscle fatigue have little effect on time-dependent increases in MSNA during light-intensity prolonged exercise.

The discrete regulation of regional vascular beds should be considered as one of the factors of baroreceptor-mediated increase in MSNA during prolonged low-intensity exercise. Cutaneous flow is controlled by both sympathetic vasoconstrictor and vasodilator nerves, but that in skeletal muscle is regulated only by the sympathetic vasoconstrictor nerves (20). During exercise, the cardiovascular system increases cardiac output and blood pressure to meet metabolic rate, which might be under baroreflex control (21). When exercise continues, body temperature increases, eliciting a decrease in vasoconstriction and an increase in vasodilation of the cutaneous vascular bed (10, 19, 28) to enhance heat dissipation. This response causes a drop in systemic blood pressure. The increased MSNA, which receives strong inhibitory input from baroreceptors (38), was seen only after the rise in body temperature during prolonged exercise and might act to compensate for thermoregulatory alterations of hemodynamics.

Several studies have shown that blood flow in nonworking as well as working muscles in both humans (10) and animals (2) decreases during dynamic exercise, coupled with an increase in body temperature (10, 19). These results suggest that enhancement of sympathetic tone of muscular beds may be modulated by elevation of body temperature, supporting our findings. On the other hand, the NE spillover increased in both active and nonactive legs, whereas blood flow in the active leg did not decrease during dynamic exercise (28). If MSNA outflow to the active and the nonactive limbs showed the same responses as seen in static muscle contraction as well as at rest (7, 33), MSNA outflow to the active muscles might also increase during exercise. Thus vascular tone in the active and resting skeletal muscle could be increased during prolonged light-intensity dynamic exercise by increased MSNA to redistribute blood to the surface for regulation of body temperature and maintenance of systemic blood pressure (19).

During muscle contraction, sympathetic outflow to the skeletal muscle has been evaluated as total activity of MSNA, i.e., represented as burst frequency multiplied by burst amplitude (14). In this study, MSNA was quantified as burst frequency alone instead of as the total activity because of technical difficulties in recording MSNA; neurograms sometimes contain unknown efferents and afferents, and motor nerve traffic due to body motion can cause changes in the intensity of MSNA burst discharges and baseline values of integrated neurograms (Fig. 1). Although the MSNA burst amplitude increased during isometric muscle contraction (14), the amplitude change was small during dynamic exercise (26). Thus burst frequency is considered a useful parameter for characterization of the intensity of MSNA response or sympathetic vasomotor tone innervating skeletal muscle during prolonged light-intensity exercise.

In summary, MSNA increased during prolonged light-intensity exercise with no elevation of blood lactate concentration and a concomitant increase in T_ty and drop in blood pressure compared with the initial phase of exercise. These results suggest that the MSNA response to exercise can be modulated by exercise duration coupled with hemodynamic changes, rather than the metaboreflex, elicited by exercise-induced body temperature elevation.

ACKNOWLEDGEMENTS

We thank Atsuko Tsukanaka, Yoji Kanao, and Isao Hasimot for technical assistance.

FOOTNOTES

Address for reprint requests: M. Saito, Applied Physiology Laboratory, Toyota Technological Institute, 2-12 Hisakata, Tempaku-ku, Nagoya 468, Japan (E-mail: msaito{at}toyota-ti.ac.jp).

Received 28 May 1996; accepted in final form 6 November 1996.

REFERENCES