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.     

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.     

Plasma norepinephrine and muscle sympathetic discharge during rhythmic exercise in humans

The purpose of this study was to examine the relationship between plasma norepinephrine concentrations (PNE) and efferent muscle sympathetic nerve activity to noncontracting muscle (MSNA) during graded, rhythmic exercise in humans. In the initial study, six healthy men (ages 20-30 yr) performed 2-min bouts of two-arm cycling exercise at power outputs of 0, 10, 20, 40, 60 (n = 6), and 80 (n = 3) W. Heart rate (HR) was recorded and intraneural measurements of MSNA (right peroneal nerve) were made continuously for 2 min before (control) and during exercise at each work load. At least 2 wk later, subjects performed the same exercise bouts at which time HR was measured and a venous (forearm) blood sample was obtained for the subsequent determination of PNE by high-performance liquid chromatography. During exercise, HR increased progressively from 0 to 80 W. Neither MSNA nor PNE increased above control in response to arm cycling at 0, 10, and 20 W [0-16 +/- 1% (SE) of peak work load], but both variables increased progressively at the 40-, 60-, and 80-W (33 +/- 1 to 67 +/- 2% of peak work load) levels (all P less than 0.05). The individual MSNA and PNE responses (% change from control) over the six work loads were directly related (r = 0.80, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle sympathetic nerve responses to physiological changes in prostaglandin production in humans.

Previous studies suggest that prostaglandins may contribute to exercise-induced increases in muscle sympathetic nerve activity (MSNA). To test this hypothesis, MSNA was measured at rest and during exercise before and after oral administration of ketoprofen, a cyclooxygenase inhibitor, or placebo. Twenty-one subjects completed two bouts of graded dynamic and isometric handgrip to fatigue. Each exercise bout was followed by 2 min of postexercise muscle ischemia. The second exercise bouts were performed after 60 min of rest in which 11 subjects were given ketoprofen (300 mg) and 10 subjects received a placebo. Ketoprofen significantly lowered plasma thromboxane B(2) in the drug group (from 36 +/- 6 to 22 +/- 3 pg/ml, P < 0.04), whereas thromboxane B(2) in the placebo group increased from 40 +/- 5 to 61 +/- 9 pg/ml from trial 1 to trial 2 (P < 0.008). Ketoprofen and placebo did not change sympathetic and cardiovascular responses to dynamic handgrip, isometric handgrip, and postexercise muscle ischemia. There was no relationship between thromboxane B(2) concentrations and MSNA or arterial pressure responses during both exercise modes. The data indicate that physiological increases or decreases in prostaglandins do not alter exercise-induced increases in MSNA and arterial pressure in humans. These findings suggest that contraction-induced metabolites other than prostaglandins mediate MSNA responses to exercise in humans.     

Influence of muscle mass on sympathetic neural activation during isometric exercise

The primary purpose of this study was to determine whether the sympathetic neural activation induced by isometric exercise is influenced by the size of the contracting muscle mass. To address this, in nine healthy subjects (aged 19-27 yr) we measured heart rate, systolic arterial blood pressure, and muscle sympathetic nerve activity in the leg (MSNA; peroneal nerve) before (control) and during 2.5 min of isometric handgrip exercise (30% of maximal voluntary force). Exercise was performed with the right and left arms separately and with both arms simultaneously (random order). During exercise, heart rate, systolic pressure, and MSNA increased above control under all conditions (P less than 0.05). For each variable, the magnitudes of the increases from control to the end of exercise were significantly greater when exercise was performed with two arms compared with either arm alone (P less than 0.05). In general, the increases in heart rate, systolic pressure, and MSNA elicited during two-arm exercise were significantly less than the simple sums of the responses evoked during exercise of each arm separately. These findings indicate that the magnitude of the sympathetic neural activation evoked during isometric exercise in humans is determined in part by the size of the active muscle mass. In addition, our results suggest that the sympathetic cardiovascular adjustments elicited during exercise of separate limbs are not simply additive but instead exhibit an inhibitory interaction (i.e., neural occlusion).     

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.     

Effect of morphine on sympathetic nerve activity in humans.

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.     

Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.     

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.     

Autonomic mediation of the pressor responses to isometric exercise in humans

The purpose of this study was to determine the respective contributions of tachycardia and increases in sympathetic nerve activity (SNA) in mediating the pressor responses to fatiguing vs. nonfatiguing levels of isometric handgrip exercise (IHE) in humans. We performed direct (microneurographic) measurements of muscle SNA from the right peroneal nerve in the leg and recorded arterial pressure (AP) and heart rate (HR) in eight healthy subjects before (control), during, and after 2.5 min of IHE at 15, 25, or 35% of maximal voluntary contraction (MVC). At 15% MVC, AP increased during the initial 1.5 min of IHE (7 mmHg, P less than 0.05) and remained at this level; at 25 and 35% MVC, AP increased throughout IHE (22 and 34 mmHg vs. control, respectively, P less than 0.05). HR increased during the initial 1.5 min of IHE at all three levels (5, 12, and 19 beats/min, respectively, P less than 0.05) but did not increase further over the last minute. At 15% MVC, muscle SNA did not increase above control; during 25 and 35% MVC, muscle SNA did not increase during the 1st min of IHE but increased progressively thereafter (109 and 205% vs. control, respectively, P less than 0.05). The magnitudes of the average increases in AP and muscle SNA over the last minute of IHE were directly related (r = 0.99, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Interactions of plasma osmolality with arterial and central venous pressures in control of sympathetic activity and heart rate in humans

Plasma osmolality alters control of sympathetic activity and heart rate in animal models; however, it is unknown whether physiological increases in plasma osmolality have such influences in humans and what effect concurrent changes in central venous and/or arterial pressures may have. We tested whether physiological increases in plasma osmolality (similar to those during exercise dehydration) alter control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) in humans. We studied 17 healthy young adults (7 women, 10 men) at baseline and during arterial pressure (AP) transients induced by sequential injections of nitroprusside and phenylephrine, under three conditions: control (C), after 1 ml/kg intravenous hypertonic saline (HT1), and after 2 ml/kg hypertonic saline (HT2). We continuously measured HR, AP, central venous pressure (CVP; peripherally inserted central catheter) and MSNA (peroneal microneurography) in all conditions. Plasma osmolality increased from 287 +/- 1 mosmol/kg in C to 290 +/- 1 mosmol/kg in HT1 (P < 0.05) but did not increase further in HT2 (291 +/- 1 mosmol/kg; P > 0.05 vs. C). Mean AP and CVP were similar between C and HT1, but both increased slightly in HT2. HR increased slightly but significantly during both HT1 and HT2 vs. C (P < 0.05). Sensitivity of baroreflex control of MSNA was significantly increased vs. C in HT1 [-7.59 +/- 0.97 (HT1) vs. -5.85 +/- 0.63 (C) arbitrary units (au).beat(-1).mmHg(-1); P < 0.01] but was not different in HT2 (-6.55 +/- 0.94 au.beat(-1).mmHg(-1)). We conclude that physiological changes in plasma osmolality significantly alter control of MSNA and HR in humans, and that this influence can be modified by CVP and AP.     

Sex differences in forebrain and cardiovagal responses at the onset of isometric handgrip exercise: a retrospective fMRI study.

In general, cardiac regulation is dominated by the sympathetic and parasympathetic nervous systems in men and women, respectively. Our recent study had revealed sex differences in the forebrain network associated with sympathoexcitatory response to baroreceptor unloading. The present study further examined the sex differences in forebrain modulation of cardiovagal response at the onset of isometric exercise. Forebrain activity in healthy men (n = 8) and women (n = 9) was measured using functional magnetic resonance imaging during 5 and 35% maximal voluntary contraction handgrip exercise. Heart rate (HR), mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA) were collected in a separate recording session. During the exercise, HR and MAP increased progressively, while MSNA was suppressed (P < 0.05). Relative to men, women demonstrated smaller HR (8 +/- 2 vs. 18 +/- 3 beats/min) and MAP (3 +/- 2 vs. 11 +/- 2 mmHg) responses to the 35% maximal voluntary contraction trials (P < 0.05). Although a similar forebrain network was activated in both groups, the smaller cardiovascular response in women was reflected in a weaker insular cortex activation. Nevertheless, men did not show a stronger deactivation at the ventral medial prefrontal cortex, which has been associated with modulating cardiovagal activity. In contrast, the smaller cardiovascular response in women related to their stronger suppression of the dorsal anterior cingulate cortex activity, which has been associated with sympathetic control of the heart. Our findings revealed sex differences in both the physiological and forebrain responses to isometric exercise.     

Skeletal muscle blood flow and flow heterogeneity during dynamic and isometric exercise in humans

The effects of dynamic and intermittent isometric knee extension exercises on skeletal muscle blood flow and flow heterogeneity were studied in seven healthy endurance-trained men. Regional muscle blood flow was measured using positron emission tomography (PET) and an [(15)O]H(2)O tracer, and electromyographic (EMG) activity was recorded in the quadriceps femoris (QF) muscle during submaximal intermittent isometric and dynamic exercises. QF blood flow was 61% (P = 0.002) higher during dynamic exercise. Interestingly, flow heterogeneity was 13% (P = 0.024) lower during dynamic compared with intermittent isometric exercise. EMG activity was significantly higher (P < 0.001) during dynamic exercise, and the change in EMG activity from isometric to dynamic exercise was tightly related to the change in blood flow in the vastus lateralis muscle (r = 0.98, P < 0.001) but not in the rectus femoris muscle (r = -0.09, P = 0.942). In conclusion, dynamic exercise causes higher and less heterogeneous blood flow than intermittent isometric exercise at the same exercise intensity. These responses are, at least partly, related to the increased EMG activity.     

Augmentation of exercise-induced muscle sympathetic nerve activity during muscle heating

Ray, Chester A., and Kathryn H. Gracey. Augmentation ofexercise-induced muscle sympathetic nerve activity during muscle heating. J. Appl. Physiol. 82(6):1719-1725, 1997.The muscle metabo- and mechanoreflexes have beenshown to increase muscle sympathetic nerve activity (MSNA) duringexercise. Group III and IV muscle afferents, which are believed tomediate this response, have been shown to be thermosensitive inanimals. The purpose of the present study was to evaluate the effect ofmuscle temperature on MSNA responses during exercise. Eleven subjectsperformed ischemic isometric handgrip at 30% of maximal voluntarycontraction to fatigue, followed by 2 min of postexercise muscleischemia (PEMI), with and without local heating of the forearm. Localheating of the forearm increased forearm muscle temperature from 34.4 ± 0.2 to 38.9 ± 0.3°C(P = 0.001). Diastolic andmean arterial pressures were augmented during exercise in the heat.MSNA responses were greater during ischemic handgrip with local heatingcompared with control (no heating) after the first 30 s. MSNA responsesat fatigue were greater during local heating. MSNA increased by 16 ± 2 and 20 ± 2 bursts per 30 s for control and heating,respectively (P = 0.03). Whenexpressed as a percent change in total activity (total burstamplitude), MSNA increased 531 ± 159 and 941 ± 237% forcontrol and heating, respectively (P = 0.001). However, MSNA was not different during PEMI between trials.This finding suggests that the augmentation of MSNA during exercisewith heat was due to the stimulation of mechanically sensitive muscleafferents. These results suggest that heat sensitizes skeletal muscleafferents during muscle contraction in humans and may play a role inthe regulation of MSNA during exercise.

     

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.     

Chemoreflex and metaboreflex control during static hypoxic exercise

To investigate the effects of muscle metaboreceptor activation during hypoxic static exercise, we recorded muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, ventilation, and blood lactate in 13 healthy subjects (22 +/- 2 yr) during 3 min of three randomized interventions: isocapnic hypoxia (10% O(2)) (chemoreflex activation), isometric handgrip exercise in normoxia (metaboreflex activation), and isometric handgrip exercise during isocapnic hypoxia (concomitant metaboreflex and chemoreflex activation). Each intervention was followed by a forearm circulatory arrest to allow persistent metaboreflex activation in the absence of exercise and chemoreflex activation. Handgrip increased blood pressure, MSNA, heart rate, ventilation, and lactate (all P < 0.001). Hypoxia without handgrip increased MSNA, heart rate, and ventilation (all P < 0.001), but it did not change blood pressure and lactate. Handgrip enhanced blood pressure, heart rate, MSNA, and ventilation responses to hypoxia (all P < 0.05). During circulatory arrest after handgrip in hypoxia, heart rate returned promptly to baseline values, whereas ventilation decreased but remained elevated (P < 0.05). In contrast, MSNA, blood pressure, and lactate returned to baseline values during circulatory arrest after hypoxia without exercise but remained markedly increased after handgrip in hypoxia (P < 0.05). We conclude that metaboreceptors and chemoreceptors exert differential effects on the cardiorespiratory and sympathetic responses during exercise in hypoxia.     

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Effect of adenosine receptor blockade with caffeine on sympathetic response to handgrip exercise in heart failure

Adenosine (Ado) increases muscle sympathetic nerve activity (MSNA) reflexively. Plasma Ado and MSNA are elevated in heart failure (HF). We tested the hypothesis that Ado receptor blockade by caffeine would attenuate reflex MSNA responses to handgrip (HG) and posthandgrip ischemia (PHGI) and that this action would be more prominent in HF subjects than in normal subjects. We studied 12 HF subjects and 10 age-matched normal subjects after either saline or caffeine (4 mg/kg) infusion during isometric [30% of maximal voluntary contraction (MVC)] and isotonic (10%, 30%, and 50%) HG exercise, followed by 2 min of PHGI. In normal subjects, caffeine did not block increases in MSNA during PHGI after 50% HG. In HF subjects, caffeine abolished MSNA responses to PHGI after both isometric and 50% isotonic exercise (P < 0.05) but MSNA responses during HG were unaffected. These findings are consistent with muscle metaboreflex stimulation by endogenous Ado during ischemic or intense nonischemic HG in HF and suggest an important sympathoexcitatory role for endogenous Ado during exercise in this condition.     

Cyclooxygenase products sensitize muscle mechanoreceptors in healthy humans

Evidence in healthy animals and humans is accumulating that the muscle mechanoreceptors play an important role in mediating sympathetic activation during exercise, especially rhythmic exercise. Furthermore, muscle mechanoreceptors appear to be sensitized acutely during exercise by metabolic by-products, although the identity of these by-products remains unknown. The purpose of this study was to determine whether the metabolic by-products 1) prostaglandins and/or 2) adenosine sensitize muscle mechanoreceptor control of muscle sympathetic nerve activity (MSNA) in normal humans during rhythmic exercise. MSNA was recorded using microneurography. Muscle mechanoreceptors were activated by low-level rhythmic forearm exercise for 3 min. In 16 healthy humans, intra-arterial indomethacin was infused into the exercising arm to inhibit synthesis of cyclooxygenase products. In 18 healthy humans, intra-arterial aminophylline was infused into the exercising arm to block adenosine receptors. During saline control, MSNA increased significantly during exercise. Inhibition of cyclooxygenase during exercise dramatically and virtually completely eliminated the reflex sympathetic activation. Inhibition of adenosine receptors with aminophylline had no effect on the sympathetic activation during muscle mechanoreceptor stimulation. In conclusion, muscle mechanoreceptors are sensitized by cyclooxygenase products, but not by adenosine, during 3 min of low-level rhythmic handgrip exercise in healthy humans. Further studies of other metabolic by-products and of patients with enhanced muscle mechanoreceptor sensitivity, such as patients with heart failure, are warranted.