The sympathetic nervous system has been long recognized as an important regulator of blood flow. Sympathetic neural activity is vital for the redistribution of blood flow and maintenance of arterial pressure during exercise. Two cardiovascular adaptations associated with exercise training are reductions in resting blood pressure (18) and increases in blood flow to active skeletal muscle (9). Reductions in sympathetic vasoconstrictor outflow following training may play an important role in both of these adaptations. Traditionally, changes in sympathetic activity to exercise training have been assessed by measuring plasma norepinephrine concentration. More recently, the norepinephrine spillover technique has been used (4). These measurements provide valuable insight on norepinephrine kinetics but do not necessarily provide an accurate assessment of efferent sympathetic nerve activity. The development of microneurography has overcome these problems by providing direct intraneural recordings of efferent sympathetic nerve activity (21). This paper will review our current understanding of the effect of exercise training on muscle sympathetic nerve activity (MSNA) at rest and during exercise. Although microneurographic recordings are limited to nonactive muscle during exercise in the studies presented, there is mounting evidence that sympathetic nerve activity to exercising muscle is comparable to that measured in the nonactive muscle (3,7,20). Additionally, we will briefly examine the effect of training on MSNA responses to other stressors (e.g., cold pressor test, lower body negative pressure).
EFFECT OF TRAINING ON RESTING MSNA
Cross-sectional studies. Most cross-sectional studies report no difference in resting MSNA between untrained and trained subjects(Table 1). However, in older trained athletes, it has been reported that they have higher resting MSNA than age-matched sedentary subjects (5). Most subjects in these studies were endurance trained.
The study by Sinoway et al. (14) is unique from the others because they compared resting MSNA between sedentary subjects and bodybuilders. Unlike endurance trained athletes, bodybuilders spend a considerable amount of time performing heavy resistance exercise. Bodybuilders had significantly higher resting MSNA than sedentary subjects. These findings suggest that heavy resistance weight training may increase resting sympathetic outflow. However, longitudinal studies using heavy resistance training will be needed before any conclusions can be made regarding sympathetic adaptations to this form of training.
Longitudinal studies. Longitudinal studies report increases, decreases, and no change in resting MSNA (Table 1). Most studies have used dynamic exercise as the training mode. Svedenhag et al.(17) was the first to examine the effect of endurance training on MSNA. They found that 8 wk of cycling at 75% of ˙VO2max four times a week failed to alter resting MSNA. One criticism of this study may be directed at the relatively small increase in ˙VO2max(≈7-8%) elicited by the training protocol. ˙VO2max is commonly used as an index for measuring training effectiveness. However, their finding was replicated by Sheldahl et al. (12) who reported no change in MSNA following a similar training protocol for 12 wk which elicited≈17% increase in ˙VO2peak. In this study, it should be noted that the subjects were older and post-training ˙VO2peak was only 35 mL·kg-1·min-1, a low value for the trained state. Ray et al. (8), in a preliminary report, found no effect on resting MSNA following one-legged training that consisted of both high-intensity interval and prolonged, continuous cycling. ˙VO2peak of the trained leg increased 20%.
In contrast to these findings, Grassi et al. (2) reported a significant decrease in resting MSNA after 10 wk of running. MSNA decreased from 21 bursts/min to 14 bursts/min after training. Training elicited a 16% increase in ˙VO2max. It should be noted that post-training ˙VO2max was only 40 mL·kg-1·min-1. Once again this value indicates that the subjects were not extremely conditioned.
Two studies used rhythmic handgrip (RHG) as their mode of training. Somers et al. (16) found that 30 sessions of RHG training performed over a 6 wk period had no affect on resting MSNA. In contrast, Sinoway et al. (13) reported that RHG training for 4 wk increased resting MSNA by 7 bursts/min. Similar training programs were used in both studies. In addition to using RHG, the exercise intensity (30-35% maximum voluntary contraction (MVC)) and the exercise endpoint (fatigue) was the same. The only noticeable difference in the training protocol was the number of contractions per minute (30 vs 12 contractions/min for Somers et al.(16) and Sinoway et al. (13), respectively). An explanation for the different results between these two studies is not apparent.
Recently, we have found that 5 wk of isometric handgrip training did not change resting MSNA (6). Despite this lack of change in MSNA, diastolic and mean arterial pressure were reduced after training.
Despite a few studies showing a possible increase(5,13,14) or decrease (2) in MSNA, there is certainly no overwhelming or convincing evidence that exercise training alters resting MSNA. A limitation of the longitudinal studies is the brevity of the training period. The longest training study was conducted by Sheldahl et al. (12) and only lasted 12 wk. It may take a longer training period to elicit adaptations in sympathetic outflow to skeletal muscle. However, the cross-sectional studies of Svedenhag et al. (17) and Seals (11) would argue against this point. Additionally, the relatively low ˙VO2max(35 to 44 mL·kg-1·min-1) obtained at the end of the endurance training programs indicate that substantial improvement in conditioning is still possible.
The significantly higher resting MSNA in bodybuilders compared with that in sedentary subjects may suggest that heavy resistance training over a period of years elevates resting MSNA. However, longitudinal studies must be conducted before any implications of heavy resistance training on autonomic regulation can be determined.
EFFECT OF TRAINING ON EXERCISING MSNA
Cross-sectional studies. Seals (11) reported no difference in MSNA responses to isometric handgrip between untrained and endurance trained subjects. The trained subjects were mainly highly fit triathletes, biathletes, cyclists, and swimmers. From the same laboratory, MSNA responses during isometric handgrip at 40% MVC in older athletes were not different from age-matched control subjects when expressed as a percent change in total activity, but was significantly greater when analyzed as an absolute change (5). Saito et al. (10) found no difference in MSNA response between the trained and contralateral forearms of racket sport players during isometric and rhythmic handgrip at 25% MVC performed to fatigue. However, when these subjects performed submaximal RHG for 10 min at 0.9 W, the exercise-induced increase in MSNA was less with the trained (dominant) forearm.
Sinoway et al. (14) reported attenuated MSNA responses in bodybuilders versus normal subjects during 2 min of isometric handgrip at 30% MVC and during ischemic RHG at 25% MVC performed to fatigue. Additionally, these investigators reported an attenuation of MSNA to isometric handgrip and posthandgrip muscle ischemia and ischemic RHG in the dominant but not nondominant forearm. The significance of this study was that changes in MSNA during exercise were not necessarily related to changes in muscle pH. For example, despite similar muscle acidosis (determined by 31P NMR spectroscopy) between the bodybuilders and normal subjects during ischemic RHG and posthandgrip muscle ischemia, MSNA responses were less in the bodybuilders. Thus, these findings indicated that possible decreases in sympathetic outflow to skeletal muscle with exercise training were related to factors besides decreases in muscle acidosis.
Longitudinal studies. Longitudinal studies have consistently shown that MSNA responses to exercise are attenuated after training(Table 1). Somers et al. (16) was the first to report that forearm training attenuated MSNA responses to exercise. The increase in MSNA during 2 min of isometric handgrip performed at 33% MVC changed from 111% before training to 38% after training with the trained forearm, whereas no significant change was reported during exercise with the sham-trained contralateral forearm. The decrease in MSNA was attributed to a decrease in the activation of the muscle metaboreflex because MSNA responses during posthandgrip muscle ischemia was attenuated following exercise with the trained but not untrained forearm. Similar conclusions were made by Ray et al.(8) who reported an attenuated MSNA response during the third minute of one-legged dynamic knee extensions at 40 W after 6 wk of one-legged cycling training. No changes in MSNA responses occurred in the contralateral untrained leg.
Sinoway et al. (13) found attenuated MSNA responses to prolonged RHG after forearm training. Similar to the findings of Somers et al.(16) and Ray et al. (8), training adaptations were specific to the trained limb. However, these investigators speculated that the smaller increase in MSNA to prolonged exercise after training was because of a change in the muscle mechanoreflex. This conclusion was based on an earlier study (1) that showed RHG performed at 25% MVC for 30 min increased MSNA but did not alter MSNA during posthandgrip muscle ischemia and did not change muscle acidosis and[H2PO4]. Both of these factors are thought to stimulate metabosensitive muscle afferents (15,19). It should be noted that resting MSNA was increased following training (17 to 25 bursts/min) and thus the decrease in MSNA responsiveness (change in burst frequency and total activity) may simply be related to the change in baseline MSNA. Based on the data provided in the paper, MSNA at the end of RHG was 28 bursts/min before and 31 bursts/min after forearm training. Despite this finding, arterial and venous plasma norepinephrine concentrations and arterial norepinephrine spillover measurements supported a decrease in sympathetic outflow to skeletal muscle during exercise.
The concept that attenuated MSNA responses to exercise are specific to muscles that have been trained is clearly supported by the above studies. Further support of this concept comes from the study of Sheldahl et al.(12). In this study, the training program consisted of both running and cycling that lasted for 12 wk. However, unlike the previous studies that examined MSNA during exercise with the trained limb, these investigators measured MSNA during isometric exercise of the untrained forearm. Not surprisingly, MSNA during isometric handgrip was unchanged. It is unfortunate that MSNA responses were not measured during any form of leg exercise. Nevertheless, these findings support the concept that the attenuation of exercise-induced increases in MSNA are specific to the trained muscle and are not generalizable to untrained muscles.
Recently, we found that, unlike RHG training which utilizes dynamic contractions, 5 wk of isometric handgrip training failed to change MSNA responses to fatiguing isometric handgrip at 30% MVC (6). This finding compared with the studies that used RHG training(13,16) indicate that dynamic exercise training is more effective than isometric exercise training in reducing MSNA responses to exercise.
The studies available do indicate that exercise training can alter MSNA responses to exercise. Currently, these studies have shown this attenuated response only during forearm exercise with the exception of a preliminary report that used leg exercise (8). This attenuation of exercise-induced increases of MSNA is specific to the trained muscles. This finding indicates that the mechanism for the attenuated MSNA response is related to alterations within the muscle (i.e., change in chemical milieu of interstitial space, decrease discharge, or desensitization of skeletal muscle afferents).
EFFECT OF TRAINING ON MSNA RESPONSES TO OTHER STRESSORS
Both cross-sectional and longitudinal training studies have examined MSNA responses to a variety of stressors. Both cross-sectional and longitudinal training studies indicate that MSNA response to a cold pressor stimulus is not changed (5,11,12). Likewise, Seals(11), in a cross-sectional study, has reported little effect of training on MSNA responses to lower body negative pressure ranging from -5 to -20 mm Hg. Sinoway et al. (14) also reported no difference in MSNA response to lower body negative pressure at -30 mm Hg between bodybuilders and normal subjects. Additionally, Sheldahl et al.(12) found no change in MSNA response to 7° head-up tilt performed for 10 min following 12 wk of endurance training.
Two studies have examined MSNA responses to baroreceptor challenges after 10-12 wk of endurance training. Sheldahl et al. (12) found no changes in MSNA response to loading and unloading of the baroreceptors by bolus injections of phenylephrine and nitroprusside after 12 wk of training. In contrast, Grassi et al. (2) reported that 10 wk of endurance training potentiated baroreceptor control of MSNA. Phenylephrine elicited greater reductions in MSNA and nitroprusside elicited greater increases in MSNA after training. It is not clear why such divergent results were found. However, it is possible that differences in the age of the subjects (Sheldahl et al.'s subjects, 54 ± 8 yr; Grassi et al.'s subects, 18 ± 1 yr) and methodology of eliciting hyper- and hypotension(bolus injection vs intravenous infusion) may account for the opposite results. More studies need to be done to clarify this important issue.
Despite the recognized importance of the sympathetic system in regulating blood flow and arterial pressure, there have been a limited number of training studies that have examined training-induced adaptations of efferent sympathetic outflow. Currently, there is no strong evidence that MSNA at rest is altered by exercise training. Two longitudinal studies that have reported a training adaptation showed opposite effects. There is, however, strong evidence that exercise-induced increases in MSNA are attenuated after training. These training adaptations appear specific to the trained muscles and not generalizable to other muscles. The mechanisms suggested for the decrease in exercise-induced MSNA are changes in both the muscle metaboreflex and muscle mechanoreflex. In addition to exercise, training has generally not altered MSNA responses to other stressors such as cold pressor test, lower body negative pressure, and upright tilting. However, the effect of training on MSNA responses to baroreceptor challenges mediated by nitroprusside and phenylephrine remain equivocal. More comprehensive training studies are needed to better understand the role of training on sympathetic neural outflow. Moreover, studies are needed to assess the effect of training-induced MSNA adaptations on skeletal muscle blood flow. Finally, sympathetic recordings to other vascular beds need to be examined before and after training (e.g., skin).
Address for correspondence: Chester A. Ray, Ph.D., Department of Exercise Science, 115 Ramsey Center, University of Georgia, Athens, GA 30602-6554. E-mail: firstname.lastname@example.org.
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