Isometric Exercise In Humans Research Articles

Central Command, but not the Muscle Metaboreflex, is Responsible for Intensity‐Dependent Increases in Muscle Sympathetic Nerve Activity to Contracting Muscle during High‐Intensity Static Isometric Exercise in Humans

Post‐exercise ischaemia has been used to demonstrate muscle metaboreflex‐mediated increases in muscle sympathetic nerve activity (MSNA) to an inactive limb during static isometric exercise. In contrast, we have previously shown a rapid centrally‐mediated increase in MSNA to a contracting leg during sustained isometric exercise, which promptly returned to resting levels at the cessation of exercise despite the presence of post‐exercise muscle ischaemia of the ipsilateral limb. However, these observations have been made during relatively low‐intensity exercise. The present study tested the hypothesis that central command, but not the muscle metaboreflex, increases MSNA to the contracting muscle during sustained isometric contractions even at higher intensities. MSNA was recorded continuously (microneurography) from the right common peroneal nerve. Twelve subjects (seven males, five females) performed two‐minute ankle dorsiflexions at 10, 20, 30, 40 and 50% of maximum voluntary contraction (MVC) ipsilateral to the MSNA recording, which was immediately followed by six minutes of post‐exercise ischaemia. There was at least six minutes rest between contractions. MSNA was analysed by measuring negative‐going cardiac‐locked sympathetic spikes from the raw neurogram. Compared with MSNA at rest (82 ± 5 spikes/min), MSNA to contracting muscle increased in an intensity‐dependent manner within one‐minute of contraction at 10 %MVC (145 ± 27 spikes/min, P=0.04), 20 %MVC (219 ± 28 spikes/min, P=0.002), 30 %MVC (480 ± 92 spikes/min, P=0.002), 40 %MVC (716 ± 185 spikes/min, P=0.01) and 50 %MVC (934 ± 275 spikes/min, P=0.02). Blood pressure increased in an intensity‐dependent manner during contractions up to 50 %MVC (76 ± 5 vs 93 ± 7 mmHg, P=0.02). Within one‐minute after each contraction MSNA returned close to resting levels even in the presence of post‐exercise ischaemia. These findings indicate that central command, and not the metaboreflex, is responsible for the increase in MSNA to contracting muscle during sustained isometric contractions, even at intensities up to 50% of MVC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Circulatory responses at the onset of handgrip exercise in patients with Parkinson's disease.

What is the central question of this study? The initial circulatory response to isometric exercise in young healthy subjects is thought to be cholinergically mediated. Do patients with Parkinson's disease, a specific population known to present cholinergic dysfunction, present impairment in these initial circulatory responses? What is the main finding and its importance? The initial reduction in total peripheral resistance was absent in patients with Parkinson's disease and in older subjects, which augmented the pressor response at the onset of isometric handgrip exercise. Given that cholinergic mechanisms play an important role in the circulatory responses at the onset of isometric exercise in humans, our data suggest that cholinergic mechanisms might be compromised with ageing. Physical exercise has been used as coping strategy for Parkinson's disease (PD). Thus, a better understanding of circulatory responses to exercise in this population is warranted. During the onset of isometric handgrip (IHG) exercise there is an increase in blood pressure (BP) and a reduction in the total peripheral resistance (TPR) in young subjects. This immediate reduction of TPR is thought to be mediated by a cholinergic mechanism. Given that PD also affects cholinergic neurons, we hypothesized that patients with PD would present blunted circulatory responses at the onset of IHG exercise. Mean BP, stroke volume, heart rate, cardiac output and TPR were measured during performance of 20s of IHG at 40% maximal voluntary contraction in 12 patients with PD (66±2years old, 171±7cm, 74±7kg), 11 older subjects (65±9years old, 171±7cm, 74±10kg) and 10 young subjects (21±1years old, 178±6cm, 79±9kg). Isometric handgrip elicited an augmented BP increase in patients with PD and older subjects at 10 and 20s compared with young subjects. However, the BP augmentation was lower at 20s in patients with PD. The IHG-induced reduction in TPR was attenuated in patients with PD and older subjects compared with young subjects. Our results show that the circulatory responses at the onset of IHG are impaired in patients with PD and older subjects. Overall, these findings suggest that the cholinergic mechanism might be compromised with ageing.

Effect of Acute Increase in Blood Pressure on Intraocular Pressure in Pigs and Humans

To study the effect on intraocular pressure (IOP) of a sudden increase in blood pressure (BP) and of changes in partial pressure of CO(2) (pCO(2)). Two experimental studies were conducted: in pigs (n = 7), where BP was reduced by intravenous injection of sodium nitroprusside and increased by injection of angiotensin II; and in humans (n = 17 healthy subjects), where BP was increased by two types of isometric exercise (squatting and handgripping) performed for 2 minutes; IOP and pCO(2) were measured every 30 seconds during separate tests (rest, hyperventilation, isometric exercise) and then after 1, 3, 6, and 10 minutes of rest. In pigs, there is a linear relationship between BP and IOP variations: DeltaIOP = 1.21 DeltaBP - 0.14 (P < 0.001). In humans, this linear relationship is as follows: DeltaIOP = 0.40 DeltaBP + 0.85 (P < 0.001) for squatting and DeltaIOP = 0.54 DeltaBP + 0.55 (P = 0.02) for handgripping. BP and IOP increases are greater with squatting than with handgripping (53% vs. 46%, P = 0.05 and 46% vs. 35%, P = 0.03, respectively). Handgripping causes a greater fall in capnia than squatting does (P = 0.02). Capnia and IOP are positively correlated (P < 0.001). The pharmacological approach in animals and the study of isometric exercise in humans show that IOP rises significantly and rapidly with kinetics close to those of BP, and the two values are linearly related. The absence of variation in capnia and the greater increase in BP during squatting may explain the greater increase in IOP during this exercise compared to handgripping.

Kinins do not alter cardiovascular and sympathetic responses to isometric exercise in humans

Bradykinin activates muscle afferents responsible for mediating the exercise pressor reflex in animals. This study was designed to test if cardiovascular and muscle sympathetic nerve activity (MSNA) responses to exercise are affected by kinins in humans. This study was conducted in a double‐blinded, placebo controlled, randomized manner. During drug treatment eight male (25±2 yr) subjects were given 20 mg of the ACE‐inhibitor quinapril to increase plasma kinins. Measurements included mean arterial blood pressure (MAP), heart rate, renal blood flow velocity (Doppler ultrasound), calf blood flow (plethysmography) and MSNA (microneurography). ACE‐inhibitor treatment lowered MAP (−9±3 mmHg) at baseline but did not alter heart rate, arterial blood pressure, renal and calf vascular conductance, and MSNA responses to ischemic isometric handgrip performed to fatigue. Cardiovascular and MSNA responses to postexercise muscle ischemia did not differ between treatments. This finding indicates that acute increases in kinins do not alter the exercise pressor reflex in humans.Research supported by NIH DC006459, HL077670, &amp; MO1RR10732

Exercise intensity influences cardiac baroreflex function at the onset of isometric exercise in humans

We sought to examine the influence of exercise intensity on carotid baroreflex (CBR) control of heart rate (HR) and mean arterial pressure (MAP) at the onset of exercise in humans. To accomplish this, eight subjects performed multiple 1-min bouts of isometric handgrip (HG) exercise at 15, 30, 45 and 60% maximal voluntary contraction (MVC), while breathing to a metronome set at eupneic frequency. Neck suction (NS) of -60 Torr was applied for 5 s at end expiration to stimulate the CBR at rest, at the onset of HG (<1 s), and after approximately 40 s of HG. Beat-to-beat measurements of HR and MAP were recorded throughout. Cardiac responses to NS at onset of 15% (-12 +/- 2 beats/min) and 30% (-10 +/- 2 beats/min) MVC HG were similar to rest (-10 +/- 1 beats/min). However, HR responses to NS were reduced at the onset of 45% and 60% MVC HG (-6 +/- 2 and -4 +/- 1 beats/min, respectively; P < 0.001). In contrast to HR, MAP responses to NS were not different from rest at exercise onset. Furthermore, both HR and MAP responses to NS applied at approximately 40s of HG were similar to rest. In summary, CBR control of HR was transiently blunted at the immediate onset of high-intensity HG, whereas MAP responses were preserved demonstrating differential baroreflex control of HR and blood pressure at exercise onset. Collectively, these results suggest that carotid-cardiac baroreflex control is dynamically modulated throughout isometric exercise in humans, whereas carotid baroreflex regulation of blood pressure is well-maintained.

Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with beta1-adrenergic blockade (metoprolol, 0.15 +/- 0.003 mg kg(-1)) or parasympathetic blockade (glycopyrrolate, 13.6 +/- 1.5 microg kg(-1)). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to -80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise (P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain (G(max)) ofthe CBR-HR function curve (-0.58 +/- 0.10 to -0.06 +/- 0.01 beats min(-1) mmHg(-1), P < 0.05), but had no effect on the G(max) of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate (P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G(max). Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.

Baroreflex resetting during exercise: mechanisms and meaning

the cardiovascular adjustments to exercise constitute well- coordinated responses throughout the body. Virtually every organ system is required to do more (e.g., skeletal muscle, the respiratory pump, and the cardiac pump) or to do the same as at rest while receiving less blood flow. Of all the

Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction with and without cardiac vagal blockade (Glycopyrrolate). CBR function was determined using rapid pulses of neck pressure and neck suction. At rest, vagal blockade nearly eliminated maximal CBR-cardiac gain (−0.71 ± 0.15 to −0.057 ± 0.01 beats min−1 mmHg−1, P < 0.05). In contrast, CBR-vasomotor function was unaltered by drug administration. During exercise the CBR-heart rate (HR) curve was reset upward and rightward in the no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate. Irrespective of drug administration exercise produced an upward and rightward resetting of the CBR control of MAP to a higher operating pressure with no change in gain. These findings demonstrate that despite marked reductions in CBR-control of HR following vagal blockade CBR control of blood pressure was well maintained. Thus, alterations in vasomotor tone are the predominant mechanism by which the baroreflex modulates blood pressure during isometric exercise. Supported in part by NIH Grant #HL-045547, the Danish National Research Foundation (504-14), a Physiological Society Travel Award and the British Heart Foundation.

Time-dependent modulation of arterial baroreflex control of muscle sympathetic nerve activity during isometric exercise in humans

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise.

Decreased muscle sympathetic nerve activity does not explain increased vascular conductance during contralateral isometric exercise in humans

At the onset of both electrically evoked (STIM) and voluntary (VOL) isometric calf exercise there is an increase in vascular conductance of the contralateral lower limb, suggesting withdrawal of muscle sympathetic nerve activity (MSNA). Seven subjects performed STIM or VOL ischaemic calf exercise at 30% maximum voluntary contraction in a seated position. Blood pressure, heart rate and peroneal MSNA in the resting contralateral lower limb were recorded. During both STIM and VOL exercise blood pressure increased (P < 0.05). Blood flow increased by 40 +/- 3 and 35 +/- 3% and conductance increased by 37 +/- 3 and 31 +/- 4% (P < 0.05) after 10 s of STIM and VOL, respectively, and thereafter declined. The time course and direction of these changes persisted with subjects in a semisupine position, confirming that the transient conductance changes were not an artefact of the dependent leg position. Thigh cuff inflation for 1 min without exercise caused a 47 +/- 7.5% (P < 0.05) reduction in MSNA, which recovered when the circulation was restored. However, when cuff inflation was followed by STIM or VOL exercise, MSNA did not fall further. These data suggest that the transient increase in vascular conductance at the onset of contralateral electrically evoked or voluntary lower limb exercise is unrelated to MSNA.

Human neuromuscular fatigue is associated with altered Na+-K+-ATPase activity following isometric exercise.

The purpose of this study was to investigate the hypothesis that reductions in Na+-K+- ATPase activity are associated with neuromuscular fatigue following isometric exercise. In control (Con) and exercised (Ex) legs, force and electromyogram were measured in 14 volunteers [age, 23.4 +/- 0.7 (SE) yr] before and immediately after (PST0), 1 h after (PST1), and 4 h after (PST4) isometric, single-leg extension exercise at ~60% of maximal voluntary contraction for 30 min using a 0.5 duty cycle (5-s contraction, 5-s rest). Tissue was obtained from vastus lateralis muscle before exercise in Con and after exercise in both the Con (PST0) and Ex legs (PST0, PST1, PST4), for the measurements of Na+-K+-ATPase activity, as determined by the 3-O-methylfluorescein phosphatase (3-O-MFPase) assay. Voluntary (maximal voluntary contraction) and elicited (10, 20, 50, 100 Hz) force was reduced 30-55% (P < 0.05) at PST0 and did not recover by PST4. Muscle action potential (M-wave) amplitude and area (measured in the vastus medialis) and 3-O-MFPase activity at PST0-Ex were less than that at PST0-Con (P < 0.05) by 37, 25, and 38%, respectively. M-wave area at PST1-Ex was also less than that at PST1-Con (P < 0.05). Changes in 3-O-MFPase activity correlated to changes in M-wave area across all time points (r = 0.38, P < 0.05, n = 45). These results demonstrate that Na+-K+- ATPase activity is reduced by sustained isometric exercise in humans from that in a matched Con leg and that this reduction in Na+-K+-ATPase activity is associated with loss of excitability as indicated by M-wave alterations.

Metabolism and inflammatory mediators in the peritendinous space measured by microdialysis during intermittent isometric exercise in humans.

1. The metabolic processes that occur around the tendon during mechanical loading and exercise are undescribed in man. These processes are important for understanding the development of overuse inflammation and injury. 2. A microdialysis technique was used to determine interstitial concentrations of glycerol, glucose, lactate, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) as well as to calculate tissue substrate balance in the peritendinous region of the human Achilles tendon. Recovery of 48-62 % (range) at rest and 70-77 % during exercise were obtained for glycerol, glucose and PGE2. 3. Six young healthy humans were studied at rest, during 30 min of intermittent static plantar flexion of the ankle at a workload corresponding to individual body weight, and during 60 min of recovery. Microdialysis was performed in both legs with simultaneous determination of blood flow by 133Xe washout in the same area, and blood sampling from the radial artery. 4. With exercise, the net release of lactate as well as of glycerol from the peritendinous space of the Achilles tendon increased 2-fold (P < 0.05). Furthermore a 100 % increase in interstitial concentration of PGE2 and TXB2 was found, but it was only significant for TXB2(P < 0.05). As peritendinous blood flow increased 2- to 3-fold during intermittent static contractions, this indicates also that the output of these substances from the tissue increased during exercise. 5. This study indicates that both lipid and carbohydrate metabolism as well as inflammatory activity is accelerated in the peritendinous region of the human Achilles tendon with dynamic loading.

Muscle cooling delays activation of the muscle metaboreflex in humans

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

Cutaneous vascular and sudomotor responses to isometric exercise in humans.

To identify whether isometric handgrip exercise (IHG) affects cutaneous vasoconstrictor and/or active vasodilator activities, seven subjects (6 men and 1 woman) performed 30% maximal voluntary contraction of a forearm under normothermic (1 bout) and hyperthermic (2 bouts) conditions. Skin blood flow was indexed by laser-Doppler flowmetry at a contralateral forearm site at which adrenergic vasoconstrictor function was blocked by iontophoresis of bretylium tosylate (BT) and therefore only has active vasodilation as a mechanism for reflex control. Skin blood flow was also monitored at an adjacent untreated site. Cutaneous vascular conductance (CVC) was calculated from the flow signal and noninvasive blood pressure. CVC was normalized to the value obtained from maximal vasodilation at that site. Sweat rate (SR) was measured at the same locations. During normothermia, IHG did not affect CVC at the control or BT-treated sites, nor did IHG affect SR (P > 0.05). The second bout of IHG in hyperthermia evoked significant reductions in CVC at the untreated (69.4 +/- 3.4 to 58.9 +/- 2.5% of maximum, P < 0.05) and BT-treated sites (75.4 +/- 6.1 to 64.4 +/- 6.2% of maximum, P < 0.05), whereas SR significantly increased (0.62 +/- 0.16 to 0.70 +/- 0.17 mg.cm-2.min-1, P < 0.05). These findings uniquely show that, in hyperthermia, IHG reduces active vasodilator activity while at the same time sudomotor activity is increasing. This suggests independent control of these effectors.

Central Command Increases Muscle Sympathetic Nerve Activity During Intense Intermittent Isometric Exercise in Humans

During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isometric handgrip at 25%, 50%, and 75% maximum voluntary contraction (MVC) in 9 human subjects with paced breathing. Similar experiments were performed in 11 additional subjects before and after partial neuromuscular blockade (intravenous curare) to isolate the influence of central command while minimizing force output and thus muscle afferent feedback. Before curare, handgrip at 25% and 50% MVC had no effect on MSNA, whereas handgrip at 75% MVC synchronized the MSNA to the handgrip such that MSNA was 5.7 +/- 1.3 times higher (mean +/- SEM, P < .001) during the contraction periods than during the relaxation periods. After curare, this synchronization of MSNA persisted without attenuation, even though force output fell to < 25% of the initial MVC. From these observations, we conclude that central command causes synchronization of motor activity and muscle sympathetic activity during intense intermittent isometric exercise.

Evaluation of spontaneous baroreflex modulation of sinus node during isometric exercise in healthy humans.

The purpose of this study was to 1) evaluate the baroreflex (BR) modulation of the sinus node during isometric exercise in humans by analyzing the variations in pulse interval (PI) in response to beat-by-beat spontaneous changes in systolic arterial pressure (SAP), thus avoiding external intervention to alter arterial pressure (AP); and to 2) evaluate the specific influence of muscle chemoreflex on the SAP-PI relationship. Sixteen healthy males were studied during rest, handgrip at 30% of maximum voluntary contraction [isometric handgrip (IHG)], post-IHG arrested forearm circulation (AFC), and recovery. AP and PI were measured continuously and noninvasively. A BR response was defined by series of at least three consecutive beats in which SAP and PI of the following beat either increased or decreased in a linear fashion. In nine subjects, forearm (FVR) and calf vascular resistances (CVR) were determined. Mean slope (by linear regression) of SAP-PI sequences did not significantly differ between rest, IHG, and AFC (14.1 +/- 2.0, 12.2 +/- 1.6, and 13.2 +/- 1.4 ms/mmHg, respectively), i.e., BR sensitivity was unchanged. IHG resulted in a rightward shift of the regression line relating SAP to PI. The shift was maintained during AFC, when PI returned to control and AP fell slightly but remained significantly elevated. CVR, which did not change during IHG, significantly increased during AFC, whereas FVR increased during both IHG and AFC, but not significantly. The data indicate that arterial BR is "reset" to a higher operating point during isometric exercise. Muscle chemoreflex appears to be partially involved in this modification.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of adenosine in the sympathetic activation produced by isometric exercise in humans.

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96 +/- 25% (n = 6, P < 0.01) and MABP by 12 +/- 3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 microgram/ml forearm per min) blocked the increase in MSNA (92 +/- 15% vs. 28 +/- 6%, n = 7, P < 0.01) and MABP (38 +/- 6 vs. 27 +/- 4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans.

Cardiopulmonary reflexes do not modulate exercise pressor reflexes during isometric exercise in humans

Previous studies that measured reflex vasoconstrictor responses during isometric exercise have suggested that these responses were modulated by arterial and cardiopulmonary baroreflexes. The purpose of these experiments was to determine forearm vasoconstrictor responses to isometric handgrip alone and during two levels of cardiopulmonary baroreceptor unloading with lower body negative pressure (-5 and -10 mmHg LBNP). Handgrip combined with -5 mmHg LBNP produced vasoconstrictor responses that were significantly greater than the algebraic sum of the separate responses to handgrip and LBNP alone, thus confirming earlier studies. However, with -10 mmHg LBNP, the vasoconstrictor responses to LBNP plus handgrip were not different from the algebraic sum of the separate response to LBNP and handgrip alone. These results indicate that when the influence of cardiac baroreceptors was reduced to a greater degree (-10 mmHg LBNP) than in previous studies, no interaction was observed, whereas with less reduction (-5 mmHg LBNP) an apparent interaction was noted. These data, together with recent studies in which sympathetic nerve activity to the lower leg was measured during similar protocols, suggest nonlinearities in the relationship between sympathetic nerve activity and vasoconstrictor responses.

Lowered cutaneous sensitivity to nonpainful electrical stimulation during isometric exercise in humans.

The effect of isometric exercise on cutaneous sensitivity to nonpainful electric stimulation was studied in human subjects. The exercises consisted of brief (duration: 1-10 s) palmar flexions of the hand or foot against varying loads (10-30% of the maximal force). A visual "go" cue was used to indicate the start and end of the exercise. Isometric hand exercise produced a load-dependent increase of electrotactile thresholds of the fingers. The threshold elevation was rapidly attenuated with prolonged duration of the exercise. The hand exercise-induced threshold elevation was of equal magnitude in the glabrous and hairy skin of the fingers. Thresholds were not changed for the hand contralateral to the exercising hand. Passive static pressure of the hand did not produce threshold changes, whereas activation of afferent inhibition by a vibrotactile stimulus (100 Hz, 0.1 mm) did produce a significant threshold elevation. Exercise-induced threshold elevation was also significant immediately prior to the EMG response of the arm but not at the time of the visual "go" signal, or before it. The threshold increase found during the EMG response was not significantly stronger than that found prior to the EMG response. These results suggest that isometric exercise load-dependently produces a phasic, rapidly attenuating increase in cutaneous tactile thresholds in the exercising limb but not multisegmentally. Corollary efferent barrage from motor to sensory structures of the brain could be underlying the threshold changes produced by isometric exercise, whereas afferent inhibitory mechanisms seem to have only a minor role.

Naloxone augments muscle sympathetic nerve activity during isometric exercise in humans

The influence of an endogenous opioid peptide (EOP) antagonist (naloxone, 1.2 mg iv bolus) on muscle sympathetic nerve activity (MSNA, microneurography) was studied on 19 young male and female volunteers. Isometric handgrip, cold pressor test, and acute baroreceptor unloading with sodium nitroprusside (autonomic stresses) were carried out under two conditions, one group (n = 11) before (control responses) and after naloxone and another group (n = 8) before and after placebo saline. Monitored cardiovascular variables included heart rate, central venous pressure (jugular vein catheter), arterial blood pressure (radial artery catheter), circulating catecholamines, and forearm blood flow. At rest, cardiovascular variables and MSNA were not affected by either naloxone or saline. MSNA (total activity = burst frequency x burst amplitude/100 cardiac cycles) increased during isometric handgrip to a greater extent (30 +/- 6 vs. 16 +/- 5 arbitrary units) after naloxone compared with control trials (P less than 0.05). After naloxone, arterial systolic and diastolic blood pressures were higher during handgrip exercise. These augmented arterial pressures and MSNA responses were not evident during either the cold pressor test or the sodium nitroprusside stress. These data suggest that isometric muscle contraction elicits a sympathetic neural response that may be modified by EOP. This interaction is not evident during two other stresses, when sympathetic responses are equal to or greater than those provoked by isometric handgrip exercise.