Different responses in skin and muscle sympathetic nerve activity to static muscle contraction

We microneurographically recorded the traffic of sympathetic nerves leading to foot volar skin activity (SSA) and leg skeletal muscle activity (MSA) during isometric handgrip and simultaneously determined sweat rate by the ventilated capsule method and skin blood flow by laser-Doppler flowmetry in the innervating area of SSA. SSA increased abruptly and was almost constant during handgrip, accompanied by an increase in sweat rate, whereas skin blood flow showed no significant change during the handgrip. MSA showed a time-dependent increase during the course of handgrip. During arterial occlusion of the working forearm after handgrip, SSA decayed to the precontraction control level, whereas MSA remained at a higher level than during control. During involuntary biceps muscle contraction induced by electrical stimulation, both SSA and MSA increased. The results suggest that the SSA response during voluntary handgrip, which was demonstrated to contain mainly sudomotor activity, might be influenced by central command and input from peripheral mechanoreceptors but be influenced little by input from muscle chemoreceptors.     

Cardiopulmonary baroreflexes do not modulate exercise-induced sympathoexcitation

The purpose of this study was to test the general hypothesis that sympathoinhibitory cardiopulmonary baroreflexes modulate sympathetic outflow during voluntary exercise in humans. Direct (microneurographic) measurements of postganglionic sympathetic nerve activity to noncontracting muscle (MSNA) were made from the right peroneal nerve in the leg, and arterial pressure (AP) and heart rate (HR) were recorded in 10 healthy subjects before (control) and for 2.5 min during each of five interventions: 1) lower-body negative pressure at -10 mmHg (LBNP) alone, 2 and 3) isometric handgrip exercise at 15 and 30% of maximal voluntary contraction (MVC) alone, and 4 and 5) handgrip at 15 and 30% MVC performed during LBNP. During LBNP alone, which should have reduced cardiopulmonary baroreflex sympathoinhibition, AP and HR did not change from control, but MSNA increased 93 +/- 24% (P less than 0.05). Handgrip elicited contraction intensity-dependent increases in AP and HR (P less than 0.05), but MSNA increased above control only at the 30% MVC level (165 +/- 30%, P less than 0.05). The HR, AP, and MSNA responses to either level of handgrip performed during LBNP were not different from the algebraic sums of the corresponding responses to handgrip and LBNP performed separately (P greater than 0.05). Since there was no facilitation of the MSNA response to handgrip when performed during LBNP compared with algebraic sums of the separate responses, our results do not support the hypothesis that cardiopulmonary baroreflexes modulate (inhibit) sympathetic outflow during exercise in humans.     

Skeletal muscle vascular responses in human limbs to isometric handgrip

Studies of whole limb blood flow have shown that static handgrip elicits a vasodilatation in the resting forearm and vasoconstriction in the resting leg. We asked if these responses occur in the skeletal muscle vascular bed, and if so, what is the relative contribution of local metabolic versus other mechanisms to these vascular responses. Blood flow recordings were made simultaneously in the skeletal muscle of the resting arm and leg using the Xenon-washout method in ten subjects during 3 min of isometric handgrip at 30% of maximal voluntary contraction. In the arm, skeletal muscle vascular resistance (SMVR) decreased transiently at the onset of exercise followed by a return to baseline levels at the end of exercise. In the leg SMVR remained unchanged during the 1st min of handgrip, but had increased to exceed baseline levels by the end of exercise. During exercise electromyography (EMG) recordings from nonexercising limbs demonstrated a progressive 20-fold increase in activity in the arm, but remained at baseline in the leg. During EMG-signal modelled exercise performed to mimic the inadvertent muscle activity, decreases in forearm SMVR amounted to 57% of the decrease seen with controlateral handgrip. The present study would seem to indicate that vascular tone in nonexercising skeletal muscle in the arm and leg are controlled differently during the early stages of static handgrip. Metabolic vasodilatation due to involuntary contraction could significantly modulate forearm skeletal muscle vascular responses, but other factors, most likely neural vasodilator mechanisms, must make major contributions. During the later stages of contralateral sustained handgrip, vascular adjustments in resting forearm skeletal muscle would seem to be the final result of reflex sympathetic vasoconstrictor drive, local metabolic vasodilator forces and possibly neurogenic vasodilator mechanisms.     

Sympathetic nerve activity related to local fatigue sensation during static contraction

The relationship between autonomic nervous activity and psychophysical responses was studied during static exercise in humans. Muscle sympathetic nerve activity (MSNA) recorded by a direct method of microneurography and the intensity of fatigue sensation in working muscles [levels of fatigue sensation (LFS) scale 0-10] were analyzed in 11 male subjects during static handgrip (SHG). SHG was exerted at a tension of 25% of maximal voluntary contraction until the given tension could no longer be sustained. MSNA, represented as total activity (burst number x mean burst amplitude), and LFS increased in a time-dependent process till the end of the SHG. At the termination of the static exercise MSNA had increased an average of 480% of the resting value. In the simple exponential curve, Y = A expBX, where X was LFS and Y was MSNA. The constants A and B estimated from the total experiments were 84.5 and 0.161, respectively. The correlation between LFS and MSNA was statistically significant. There was a large difference in the value of constant B (0.089-0.278) among the subjects, and a relatively small difference in the value of constant A (37.5-133.8). The increases in both MSNA and LFS during SHG may be mainly related to the same afferent volley from working skeletal muscles. The results indicate that the response of the muscle sympathetic nerve to SHG relates to the psychological feelings of fatigue in the working muscles.     

Sympathetic neural discharge and vascular resistance during exercise in humans

The purpose of this study was to determine the relationship between changes in efferent muscle sympathetic nerve activity (MSNA) to the lower leg and calf vascular resistance (CVR) during isometric exercise in humans. We made intraneural (microneurographic) determinations of MSNA in the right leg (peroneal nerve) while simultaneously measuring calf blood flow to the left leg, arterial pressure, and heart rate in 10 subjects before (control), during, and after (recovery) isometric handgrip exercise performed for 2.5 min at 15, 25, and 35% of maximal voluntary contraction (MVC). Heart rate and arterial pressure increased above control within the initial 30 s of handgrip at all levels, and the magnitudes of the increases at end contraction were proportional to the intensity of the exercise. In general, neither MSNA nor CVR increased significantly above control levels during handgrip at 15% MVC. Similarly, neither variable increased above control during the initial 30 s of handgrip at 25 and 35% MVC; however, during the remainder of the contraction period, progressive, parallel increases were observed in MSNA and CVR (P less than 0.05). The correlation coefficients relating changes in MSNA to changes in CVR for the individual subjects averaged 0.63 +/- 0.07 (SE) (range 0.30-0.91) and 0.94 +/- 0.06 (range 0.80-0.99) for the 25 and 35% MVC levels, respectively. During recovery, both MSNA and CVR returned rapidly toward control levels. These findings demonstrate that muscle sympathetic nerve discharge and vascular resistance in the lower leg are tightly coupled during and after isometric arm exercise in humans. Furthermore, the exercise-induced adjustments in the two variables are both contraction intensity and time dependent.     

Changes in muscle sympathetic nerve activity and calf blood flow during static handgrip exercise

To test the function of sympathetic vasco-constrictor nerves on blood flow in resting limbs during static muscle contraction, muscle sympathetic nerve activity (MSNA) to the leg muscle was recorded from the tibial nerve microneurographically before, during and after 2 min of static handgrip (SHG). Simultaneously, calf blood flow (CBF) was measured by strain gauge plethysmography. An increase in MSNA, a decrease in CBF and an increase in calf vascular resistance (CVR) in the same resting limb occurred concomitantly during SHG. However, the increase in CVR was blunted in the second minute of handgrip when MSNA was still increasing. The results indicated that the decrease of CBF during SHG reflects the increase in MSNA, while the dissociation between MSNA and CVR at the later period of SHG may be related to metabolic change produced by the vasoconstriction.     

Ischemic exercise and the muscle metaboreflex.

In exercising muscle, interstitial metabolites accumulate and stimulate muscle afferents. This evokes the muscle metaboreflex and raises arterial blood pressure (BP). In this report, we examined the effects of tension generation on muscle metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR), BP, P(i), H(2)PO(4)(-), and pH ((31)P-NMR spectroscopy) data were collected in 10 normal healthy men (age 23 +/- 1 yr) during rhythmic handgrip exercise. After baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2 min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was continued until near fatigue (Borg 19). Measurements were continued for an additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60% of the subjects' maximum voluntary contraction (MVC) in random order. As tension increased, the time to fatigue decreased. In addition, mean arterial pressure and HR were higher at 60% MVC than at any of the other lower tensions. The NMR data showed significantly greater increases in H(2)PO(4)(-), P(i), and H(+) at 60% than at 15 and 30% MVC. Therefore, despite the subjects working to the same perceived effort level, a greater reflex response (represented by BP and HR data) was elicited at 60% MVC than at any of the other ischemic tensions. These data are consistent with the hypothesis that, as tension increases, factors aside from insufficient blood flow contribute to the work effect on muscle metabolites and the magnitude of the reflex response.     

The influence of straining maneuvers on the pressor response during isometric exercise

Experiments were performed to determine to what extent increments in esophageal and abdominal pressure would have on arterial blood pressure during fatiguing isometric exercise. Arterial blood pressure was measured during handgrip and leg isometric exercise performed with both a free and occluded circulation to active muscles. Handgrip contractions were exerted at 33 and 70% MVC (maximum voluntary contraction) by 4 volunteers in a sitting position and calf muscle contractions at 50 and 70% MVC with the subjects in a kneeling position. Esophageal pressure measured at the peak of inspirations did not change during either handgrip or leg contractions but peak expiratory pressures increased progressively during both handgrip and leg contractions as fatigue occurred. These increments were independent of the tensions of the isometric contractions exerted. Intra-abdominal pressures measured at the peak of either inspiration or expiration did not change during inspiration with handgrip contractions but increased during expiration. During leg exercise, intraabdominal pressures increased during both inspiration and expiration, reaching peak levels at fatigue. The arterial blood pressure also reached peak levels at fatigue, independent of circulatory occlusion and tension exerted, averaging 18.5-20 kPa (140-150 mm Hg) for both handgrip and leg contractions. While blood pressure returned to resting levels following exercise with a free circulation, it declined by only 2.7-3.8 kPa after leg and handgrip exercise, respectively, during circulatory occlusion. These results indicate that straining maneuvers contribute 3.5 to 7.8 kPa to the change in blood pressure depending on body position.     

Hyperoxia enhances metaboreflex sensitivity during static exercise in humans

Peripheral chemoreflex inhibition with hyperoxia decreases sympathetic nerve traffic to muscle circulation [muscle sympathetic nerve activity (MSNA)]. Hyperoxia also decreases lactate production during exercise. However, hyperoxia markedly increases the activation of sensory endings in skeletal muscle in animal studies. We tested the hypothesis that hyperoxia increases the MSNA and mean blood pressure (MBP) responses to isometric exercise. The effects of breathing 21% and 100% oxygen at rest and during isometric handgrip at 30% of maximal voluntary contraction on MSNA, heart rate (HR), MBP, blood lactate (BL), and arterial O2 saturation (SaO2) were determined in 12 healthy men. The isometric handgrips were followed by 3 min of postexercise circulatory arrest (PE-CA) to allow metaboreflex activation in the absence of other reflex mechanisms. Hyperoxia lowered resting MSNA, HR, MBP, and BL but increased Sa(O2) compared with normoxia (all P < 0.05). MSNA and MBP increased more when exercise was performed in hyperoxia than in normoxia (MSNA: hyperoxic exercise, 255 +/- 100% vs. normoxic exercise, 211 +/- 80%, P = 0.04; and MBP: hyperoxic exercise, 33 +/- 9 mmHg vs. normoxic exercise, 26 +/- 10 mmHg, P = 0.03). During PE-CA, MSNA and MBP remained elevated (both P < 0.05) and to a larger extent during hyperoxia than normoxia (P < 0.05). Hyperoxia enhances the sympathetic and blood pressure (BP) reactivity to metaboreflex activation. This is due to an increase in metaboreflex sensitivity by hyperoxia that overrules the sympathoinhibitory and BP lowering effects of chemoreflex inhibition. This occurs despite a reduced lactic acid production.     

Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.     

Weight loss improves neurovascular and muscle metaboreflex control in obesity

We studied the effects of a hypocaloric diet (D, n = 24, age: 32.2 +/- 1.4 yr, body mass index: 34.7 +/- 0.5 kg/m2) and a hypocaloric diet associated with exercise training (D + T, n = 25, age: 32.3 +/- 1.3 yr, body mass index: 32.9 +/- 0.4 kg/m2) on muscle metaboreflex control, muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, and forearm blood flow (plethysmography) levels during handgrip exercise at 10% and 30% of maximal voluntary contraction in normotensive obese women. An additional 10 women matched by age and body mass index were studied as a nonadherent group. D or D + T significantly decreased body mass index. D or D + T significantly decreased resting MSNA (bursts/100 heartbeats). The absolute levels of MSNA were significantly lower throughout 10% and 30% exercise after D or D + T, although no change was found in the magnitude of response of MSNA. D + T, but not D, significantly increased resting forearm vascular conductance. D + T significantly increased the magnitude of the response of forearm vascular conductance during 30% exercise. D or D + T significantly increased MSNA levels during posthandgrip circulatory arrest when muscle metaboreflex is isolated. In conclusion, weight loss improves muscle metaboreflex control in obese women. Weight loss reduces MSNA, which seems to be centrally mediated. Weight loss by D + T increases forearm vascular conductance at rest and during exercise in obese individuals.     

Sympathetic outflow enhances the stretch reflex response in the relaxed soleus muscle in humans.

Animal experiments suggest that an increase in sympathetic outflow can depress muscle spindle sensitivity and thus modulate the stretch reflex response. The results are, however, controversial, and human studies have failed to demonstrate a direct influence of the sympathetic nervous system on the sensitivity of muscle spindles. We studied the effect of increased sympathetic outflow on the short-latency stretch reflex in the soleus muscle evoked by tapping the Achilles tendon. Nine subjects performed three maneuvers causing a sustained activation of sympathetic outflow to the leg: 3 min of static handgrip exercise at 30% of maximal voluntary contraction, followed by 3 min of posthandgrip ischemia, and finally during a 3-min mental arithmetic task. Electromyography was measured from the soleus muscle with bipolar surface electrodes during the Achilles tendon tapping, and beat-to-beat changes in heart rate and mean arterial blood pressure were monitored continuously. Mean arterial pressure was significantly elevated during all three maneuvers, whereas heart rate was significantly elevated during static handgrip exercise and mental arithmetic but not during posthandgrip ischemia. The peak-to-peak amplitude of the short-latency stretch reflex was significantly increased during mental arithmetic (P < 0.05), static handgrip exercise (P < 0.001), and posthandgrip ischemia (P < 0.005). When expressed in percent change from rest, the mean peak-to-peak amplitude increased by 111 (SD 100)% during mental arithmetic, by 160 (SD 103)% during static handgrip exercise, and by 90 (SD 67)% during posthandgrip ischemia. The study clearly indicates a facilitation of the short-latency stretch reflex during increased sympathetic outflow. We note that the enhanced stretch reflex responses observed in relaxed muscles in the absence of skeletomotor activity support the idea that the sympathetic nervous system can exert a direct influence on the human muscle spindles.     

Limb congestion enhances the synchronization of sympathetic outflow with muscle contraction

In this report, we examined if the synchronization of muscle sympathetic nerve activity (MSNA) with muscle contraction is enhanced by limb congestion. To explore this relationship, we applied signal-averaging techniques to the MSNA signal obtained during short bouts of forearm contraction (2-s contraction/3-s rest cycle) at 40% maximal voluntary contraction for 5 min. We performed this analysis before and after forearm venous congestion; an intervention that augments the autonomic response to sustained static muscle contractions via a local effect on muscle afferents. There was an increased percentage of the MSNA noted during second 2 of the 5-s contraction/rest cycles. The percentage of total MSNA seen during this particular second increased from minute 1 to 5 of contraction and was increased further by limb congestion (control minute 1 = 25.6 +/- 2.0%, minute 5 = 32.8 +/- 2.2%; limb congestion minute 1 = 29.3 +/- 2.1%, minute 5 = 37.8 +/- 3.9%; exercise main effect <0.005; limb congestion main effect P = 0.054). These changes in the distribution of signal-averaged MSNA were seen despite the fact that the mean number of sympathetic discharges did not increase over baseline. We conclude that synchronization of contraction and MSNA is seen during short repetitive bouts of handgrip. The sensitizing effect of contraction time and limb congestion are apparently due to feedback from muscle afferents within the exercising muscle.     

Differences in muscle sympathetic nerve response to isometric exercise in different muscle groups

The aim of this study was to examine the effects of muscle fibre composition on muscle sympathetic nerve activity (MSNA) in response to isometric exercise. The MSNA, recorded from the tibial nerve by a microneurographic technique during contraction and following arterial occlusion, was compared in three different muscle groups: the forearm (handgrip), anterior tibialis (foot dorsal contraction), and soleus muscles (foot plantar contraction) contracted separately at intensities of 20%, 33% and 50% of the maximal voluntary force. The increases in MSNA relative to control levels during contraction and occlusion were significant at all contracting forces for handgrip and at 33% and 50% of maximal for dorsal contraction, but there were no significant changes, except during exercise at 50%, for plantar contraction. The size of the MSNA response correlated with the contraction force in all muscle groups. Pooling data for all contraction forces, there were different MSNA responses among muscle groups in contraction forces (P = 0.0001, two-way analysis of variance), and occlusion periods (P = 0.0001). The MSNA increases were in the following order of magnitude: handgrip, dorsal, and plantar contractions. The order of the fibre type composition in these three muscles is from equal numbers of types I and II fibres in the forearm to increasing number of type I fibres in the leg muscles. The different MSNA responses to the contraction of different muscle groups observed may have been due in part to muscle metaboreflex intensity influenced by their metabolic capacity which is related to by their metabolic capacity which is related to the fibre type.     

Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.     

Isometric exercise modifies autonomic baroreflex responses in humans

The influence of brief, moderate isometric exercise on the earliest vagal and sympathetic responses to changes of afferent carotid baroreceptor activity was studied in 10 healthy young men and women. Vagal-cardiac nerve activity was estimated from changes of electrocardiographic R-R intervals, and postganglionic peroneal nerve muscle sympathetic activity was measured directly from microneurographic recordings. Carotid baroreceptor activity was altered with 5-s periods of 30 Torr pressure or suction applied to a neck chamber during held expiration. Brief handgrip (30% of maximum) significantly reduced base-line R-R intervals, did not modify reductions of R-R intervals during neck pressure, and significantly reduced increases of R-R intervals during neck suction. Handgrip did not significantly increase base-line sympathetic activity from resting levels, but it significantly diminished increases of sympathetic activity during neck pressure and augmented reductions of sympathetic activity during neck suction. Our results suggest that exercise modifies, in small but significant ways, early sympathetic and vagal responses to abrupt changes of arterial baroreceptor input in humans.     

Impact of heart failure and exercise capacity on sympathetic response to handgrip exercise

Peak oxygen uptake (VO(2 peak)) in patients with heart failure (HF) is inversely related to muscle sympathetic nerve activity (MSNA) at rest. We hypothesized that the MSNA response to handgrip exercise is augmented in HF patients and is greatest in those with low VO(2 peak). We studied 14 HF patients and 10 age-matched normal subjects during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50% MVC) handgrip exercise that was followed by 2 min of posthandgrip ischemia (PHGI). MSNA was significantly increased during exercise in HF but not normal subjects. Both MSNA and HF levels remained significantly elevated during PHGI after 30% isometric and 50% isotonic handgrip in HF but not normal subjects. HF patients with lower VO(2 peak) (<56% predicted; n = 8) had significantly higher MSNA during rest and exercise than patients with VO(2 peak) > 56% predicted (n = 6) and normal subjects. The muscle metaboreflex contributes to the greater reflex increase in MSNA during ischemic or intense nonischemic exercise in HF. This occurs at a lower threshold than normal and is a function of VO(2 peak).     

Forearm endurance training attenuates sympathetic nerve response to isometric handgrip in normal humans.

Recent evidence indicates that muscle ischemia and activation of the muscle chemoreflex are the principal stimuli to sympathetic nerve activity (SNA) during isometric exercise. We postulated that physical training would decrease muscle chemoreflex stimulation during isometric exercise and thereby attenuate the SNA response to exercise. We investigated the effects of 6 wk of unilateral handgrip endurance training on the responses to isometric handgrip (IHG: 33% of maximal voluntary contraction maintained for 2 min). In eight normal subjects the right arm underwent exercise training and the left arm sham training. We measured muscle SNA (peroneal nerve), heart rate, and blood pressure during IHG before vs. after endurance training (right arm) and sham training (left arm). Maximum work to fatigue (an index of training efficacy) was increased by 1,146% in the endurance-trained arm and by only 40% in the sham-trained arm. During isometric exercise of the right arm, SNA increased by 111 +/- 27% (SE) before training and by only 38 +/- 9% after training (P less than 0.05). Endurance training did not significantly affect the heart rate and blood pressure responses to IHG. We also measured the SNA response to 2 min of forearm ischemia after IHG in five subjects. Endurance training also attenuated the SNA response to postexercise forearm ischemia (P = 0.057). Sham training did not significantly affect the SNA responses to IHG or forearm ischemia. We conclude that endurance training decreases muscle chemoreflex stimulation during isometric exercise and thereby attenuates the sympathetic nerve response to IHG.     

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.     

The activity of a single muscle sympathetic vasoconstrictor nerve unit is affected by physiological stress in humans

Recording of neural firing from single-unit muscle sympathetic nerve activity (MSNA) is a new strategy offering information about the frequency of pure sympathetic firing. However, it is uncertain whether and when single-unit MSNA would be more useful than multiunit MSNA for analysis of various physiological stresses in humans. In 15 healthy subjects, we measured single-unit and multiunit MSNA before and during handgrip exercise at 30% of maximum voluntary contraction for 3 min and during the Valsalva maneuver at 40 mmHg expiratory pressure for 15 s. Shapes of individual single-unit MSNA were proved to be consistent and suitable for further evaluation. Single-unit and multiunit MSNA exhibited similar responses during handgrip exercise. However, acceleration of neural firing determined from single-unit MSNA became steeper than multiunit MSNA during the Valsalva maneuver. During the Valsalva maneuver, unlike handgrip exercise, the distribution of multiunit burst between 0, 1, 2, 3, and 4 spikes was significantly shifted toward multiple spikes within a given burst (P < 0.05). These results indicated that evaluation of single-unit MSNA could provide more detailed and accurate information concerning the role and responses of neuronal discharges induced by various physiological stresses in humans, especially amid intense sympathetic activity.