Muscle Metaboreceptor Activation Research Articles

The effect of muscle metaboreflex on the distribution of blood flow in cerebral arteries during isometric exercise.

The present study examined the effect of muscle metaboreflex on blood flow in different cerebral arteries. Eleven healthy participants performed isometric, one-leg knee extension at 30% maximal voluntary contraction for 2min. Activated muscle metaboreflex was isolated for 2min by post-exercise muscle ischemia (PEMI). The contralateral internal carotid (ICA), vertebral (VA), and ipsilateral external carotid arteries (ECA) blood flows were evaluated using Doppler ultrasound. The ICA blood flow increased at the beginning of exercise (P = 0.004) but returned to the baseline level at the end of exercise (P = 0.055). In contrast, the VA blood flow increased and it was maintained until the end of the exercise (P = 0.011), while the ECA blood flow gradually increased throughout the exercise (P = 0.001). These findings indicate that isometric exercise causes a heterogeneous cerebral blood flow response in different cerebral arteries. During PEMI, the conductance of the VA as well as that of the ICA was significantly lower compared with the baseline value (P = 0.020 and P = 0.032, at PEMI90), while the conductance of the ECA was not different from the baseline (P = 0.587), suggesting that the posterior and anterior cerebral vasculature were similarly affected during exercise by activation of muscle metaboreceptors, but not in the non-cerebral artery. Since ECA branches from ICA, the balance in the different influence of muscle metaboreflex on ECA (vasodilation via exercise-induced hypertension) and ICA (vasoconstriction) may contribute to the decrease in ICA blood flow at the end of isometric exercise.

Postexercise whole-body sweating increases during muscle metaboreceptor activation in young men.

We assessed the effect of metaboreceptor activation on whole-body evaporative heat loss (WB-EHL) in 12 men (aged 24 ± 4 years) in the early-to-late stages of a 60-min exercise recovery in the heat. Metaboreceptor activation induced by 1-min isometric-handgrip (IHG) exercise followed by 5-min forearm ischemia to trap metabolites increased WB-EHL by 25%-31% and 26%-34% during the ischemic period relative to IHG-only and control (natural recovery only), respectively, throughout recovery. We show that metaboreceptor activation enhances WB-EHL in recovery.

Postexercise Activation of Muscle Metaboreceptors Modulates Whole-Body Evaporative Heat Loss

Postexercise Activation of Muscle Metaboreceptors Modulates Whole-Body Evaporative Heat Loss

Influence of forearm muscle metaboreceptor activation on sweating and cutaneous vascular responses during dynamic exercise.

We examined whether the sustained activation of metaboreceptor in forearm during cycling exercise can modulate sweating and cutaneous vasodilation. On separate days, 12 young participants performed a 1.5-min isometric handgrip exercise at 40% maximal voluntary contraction followed by 1) 9-min forearm ischemia (Occlusion, to activate metaboreceptor) or 2) no ischemia (Control) in thermoneutral conditions (27°C, 50%) with mean skin temperature clamped at 34°C. Thirty seconds after the handgrip exercise, participants cycled for 13.5 min at 40% V̇o2 max For Occlusion, forearm ischemia was maintained for 9 min followed by no ischemia thereafter. Local sweat rate (SR, ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) on the contralateral nonischemic arm as well as esophageal and skin temperatures were measured continuously. The period of ischemia in the early stages of exercise increased SR (+0.03 mg·cm(-2)·min(-1), P < 0.05) but not CVC (P > 0.05) above Control levels. No differences were measured in the esophageal temperature at which onset of sweating (Control 37.19 ± 0.09 vs. Occlusion 37.07 ± 0.09°C) or CVC (Control 37.21 ± 0.08 vs. Occlusion 37.08 ± 0.10°C) as well as slopes for these responses (all P > 0.05). However, a greater elevation in SR occurred thereafter such that SR was significantly elevated at the end of the ischemic period relative to Control (0.37 ± 0.05 vs. 0.23 ± 0.05 mg·cm(-2)·min(-1), respectively, P < 0.05) despite no differences in esophageal temperature. We conclude that the activation of forearm muscle metaboreceptor can modulate sweating, but not CVC, during cycling exercise without affecting the core temperature-SR relationship.

The Mechanisms Underlying the Muscle Metaboreflex Modulation of Sweating and Cutaneous Vascular Conductance in Passively Heated Humans

Previous reports demonstrate that the nonthermal muscle metaboreflex increases sweating and reduces cutaneous perfusion during heat stress. However the mechanisms mediating these responses remain unknown. Given that nitric oxide synthase (NOS) and cyclooxygenase (COX) contribute to the sweating response during heat stress, these enzymes may also play a role in the metaboreflex‐induced increases in sweating during heat stress. Additionally, NOS, COX, and adenosine receptors contribute to cutaneous vascular responses during heat stress. Thus these factors may be involved in reducing cutaneous perfusion in response to metaboreceptor activation during heat stress. Eleven healthy males (31 ± 13 years) donned a water‐perfused suit whereby mean skin temperature was clamped to ~35 °C (pre‐heating; to activate sweating without changes in core temperature) which was followed by a period of whole‐body heating to induce and maintain a 1.0 °C increase in core temperature (post‐heating) above pre‐heating levels. Participants performed the metaboreceptor activation protocol [1 min bout of isometric handgrip (IHG) exercise at 60% of their maximal voluntary contraction followed by 3 min of forearm occlusion (OCC; to stimulate metaboreceptors)] twice at each heating phase (pre‐heating: IHG+OCC‐1 and ‐2; and post‐heating: IHG+OCC‐3 and ‐4), each separated by 10 min. Prior to the start of the trial, participants were instrumented with four intradermal microdialysis fibres in the forearm skin that were continuously perfused with (1) lactated Ringer solution (Control), (2) 10 mM NG‐nitro‐L‐arginine methylester (L‐NAME; a non‐selective NOS inhibitor), (3) 10 mM ketorolac (KETO; a non‐selective COX inhibitor), or (4) 4 mM theophylline (THEO; a non‐selective adenosine receptor antagonist). Forearm sweat rate (ventilated capsule; n=9) and cutaneous vascular conductance (CVC; perfusion units divided by mean arterial pressure, n=9) were measured at each of the four skin sites. For all sites, sweating increased and remained elevated during IHG and OCC respectively, regardless of the level of hyperthermia (all P&lt; 0.05). The increase in sweat rate from pre‐IHG levels during IHG+OCC‐2 and IHG+OCC‐3 measured at the Control (0.26 ± 0.14 and 0.03 ± 0.01 mg· min−1· cm−2, respectively) was partially attenuated by NOS inhibition (23 ± 23 and 22 ± 26%, respectively, P&lt;0.05). During the pre‐heating phase, no influence of IHG+OCC‐1 or ‐2 was observed on CVC (all P&gt;0.05). Moreover, relative to pre‐IHG levels, CVC was reduced during IHG+OCC‐3 at Control (IHG; −9.4 ± 8.2 and OCC; −3.2 ± 3.2 %CVCmax, P&lt;0.05). Additionally, at all sites compared to Control, there were no differences in CVC during IHG+OCC at each heating phase (all P&gt;0.05). We show that during heat stress NOS, but not COX and adenosine receptors, contributes to the sweating response to muscle metaboreceptor activation, whereas CVC is not modulated by NOS, COX, and adenosine receptors.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).

Modulation of muscle metaboreceptor activation upon sweating and cutaneous vascular responses to rising core temperature in humans.

The present study investigated the role of muscle metaboreceptor activation on human thermoregulation by measuring core temperature thresholds and slopes for sweating and cutaneous vascular responses during passive heating associated with central and peripheral mechanisms. Six male and eight female subjects inserted their lower legs into hot water (43°C) while wearing a water perfusion suit on the upper body (34°C). One minute after immersion, an isometric handgrip exercise--40% of maximum voluntary contraction-was conducted for 1.5 min in both control and experimental conditions, while postexercise occlusion was performed in the experimental condition only for 9 min. The postexercise forearm occlusion during passive heating consistently stimulated muscle metaboreceptors, as implicated by significantly elevated mean arterial blood pressure throughout the experimental period (P <0.05). Stimulation of the forearm muscle metaboreceptors increased sweating and cutaneous vascular responses during passive heating, and was associated with significant reductions in esophageal temperature threshold of sweating and cutaneous vasodilation (Δ threshold, sweating: 0.33 ± 0.05 and 0.16 ± 0.04°C, cutaneous vascular conductance: 0.38 ± 0.08 and 0.16 ± 0.05°C for control and experimental groups, respectively, P < 0.05). The slopes of these responses were not different between the conditions. These results suggest that muscle metaboreceptor activation in the forearm accelerates sweating and cutaneous vasodilation during passive heating associated with a reduction in core temperature thresholds and may be related to central mechanisms controlling heat loss responses.

Effect of muscle metaboreflex activation on central hemodynamics and cardiac function in humans

We sought to determine how the mode of muscle metaboreflex activation influences the central hemodynamic response and cardiac inotropic and lusotropic function in healthy humans. Ten healthy males performed (i) isometric handgrip (IHG) with and without post-exercise ischemia (PEI) to examine the influence of isolated muscle metaboreflex activation and (ii) rhythmic handgrip (RHG) with and without ischemia to examine the influence of enhanced muscle metaboreflex activation. Heart rate (HR) and blood pressure (BP) were continuously monitored. Stroke volume (SV, Doppler echocardiography) was measured, cardiac output (CO = HR × SV) and total peripheral resistance (TPR = mean BP/CO) calculated, and indices of left ventricular systolic and diastolic function were obtained (tissue Doppler imaging). During isolated muscle metaboreflex activation with PEI following IHG, mean BP (+23 ± 3 mm Hg) and TPR were elevated from baseline (p < 0.05), whereas HR, SV, and CO were unchanged. Enhanced muscle metaboreceptor activation during ischemic RHG augmented the increase in mean BP, CO, and HR (p < 0.05 ischemic vs. free-flow RHG), whereas SV and TPR were unchanged from baseline. Neither isolated (PEI) nor enhanced muscle metaboreflex activation altered left ventricular systolic function (systolic myocardial velocity), but left atrial systolic function (late diastolic myocardial velocity) was enhanced. These findings indicate that the mode of muscle metaboreceptor activation (during vs. post handgrip) determines whether the resultant pressor response is flow (CO) or vasoconstriction (TPR) mediated, and that although left ventricular systolic function is unchanged, enhanced left atrial systolic function likely aids the preservation of SV during muscle metaboreflex engagement.

Sweating response to passive stretch of the calf muscle during activation of forearm muscle metaboreceptors in heated humans

Activation of muscle metaboreceptors and mechanoreceptors has been shown to independently influence the sweating response, while their integrative control effects remain unclear. We examined the sweating response when the two muscle receptors are concurrently activated in different limbs, as well as the blood pressure response. In total, 27 young males performed passive calf muscle stretches (muscle mechanoreceptor activation) for 30 s in a semisupine position with and without postisometric handgrip exercise muscle ischemia (PEMI, muscle metaboreceptor activation) at exercise intensities of 35 and 50% of maximum voluntary contraction (MVC) under hot conditions (ambient temperature, 35°C, relative humidity, 50%). Passive calf muscle stretching alone increased the mean sweating rate significantly on the forehead, chest, and thigh (SRmean) and mean arterial blood pressure (MAP), but not the heart rate (HR), from prestretching levels by 0.04 ± 0.01 mg·cm(2)·min(-1), 4.0 ± 1.3 mmHg (P < 0.05), and -1.0 ± 0.5 beats/min (P > 0.05), respectively. The SRmean and MAP during PEMI were significantly higher than those at rest. The passive calf muscle stretch during PEMI increased MAP significantly by 3.4 ± 1.0 and 2.0 ± 0.7 mmHg for 35 and 50% of MVC, respectively (P < 0.05), but not that of SRmean or HR at either exercise intensity. These results suggest that sweating and blood pressure responses to concurrent activation of the two muscle receptors in different limbs differ and that the influence of calf muscle mechanoreceptor activation alone on the sweating response disappears during forearm muscle metaboreceptor activation.

Autonomic control of the heart during exercise in humans: role of skeletal muscle afferents

What is the topic of this review? The autonomic nervous system plays a key role in bringing about the cardiovascular responses to exercise necessitated by the increased metabolic requirements of the active skeletal muscle. The complex interaction of central and peripheral neural control mechanisms evokes a decrease in parasympathetic activity and an increase sympathetic activity to the heart during exercise. What advances does it highlight? This review presents some of the recent insights provided by human studies into the role of mechanically and metabolically sensitive skeletal muscle afferents in the regulation of cardiac autonomic control during exercise. The autonomic responses to exercise are orchestrated by the interactions of several central and peripheral neural mechanisms. This report focuses on the role of peripheral feedback from skeletal muscle afferents in the autonomic control of the heart during exercise in humans. Heart rate responses to passive calf stretch are abolished with cardiac parasympathetic blockade, indicating that the activation of mechanically sensitive skeletal muscle afferents (muscle mechanoreceptors) can inhibit cardiac parasympathetic activity and is likely to contribute to the increase in heart rate at the onset of exercise. Recent experiments show that the partial restriction of blood flow to the exercising skeletal muscles, to augment the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreceptors) in humans, evokes an increase in heart rate that is attenuated with β1-adrenergic blockade, thus suggesting that this response is principally mediated via an increase in cardiac sympathetic activity. Heart rate remains at resting levels during isolated activation of muscle metaboreceptors with postexercise ischaemia following hand grip, unless cardiac parasympathetic activity is inhibited, whereupon a sympathetically mediated increase in heart rate is unmasked. During postexercise ischaemia following leg cycling exercise, heart rate appears to remain elevated due to withdrawal of parasympathetic tone and/or the activation of sympathetic activity to the heart. Although the importance of skeletal muscle afferent feedback to the autonomic control of the heart during exercise is incontrovertible, the complexity of cardiac sympathetic-parasympathetic interactions and the absence of direct intraneural recordings in humans mean that it remains incompletely understood.

Baroreceptors and thermal state modulate metaboreceptor reductions in local heat loss responses

Studies show that activation of muscle metaboreceptors following isometric hand grip exercise (IHG) attenuates local sweating (LSR) and cutaneous vascular conductance (CVC). It is unclear however if: 1) concomitant changes in baroreceptor loading status and/or, 2) the level of thermal stress modulates this response. Twelve males performed 1-min of IHG at 60% of maximal voluntary contraction followed by 2-min of ischemia under simultaneous application of either lower body positive (LBPP, +40 mmHg), negative (LBNP, −20 mmHg) or no pressure (CON). On separate days, trials were repeated under no heat stress (NHS) and heat stress conditions of 0.6°C (MHS) and 1.2°C (HHS) increase in esophageal temperature (Tes). For all heat stress conditions, mean arterial pressure (MAP) remained greater during LBPP (p<0.001), and lower during LBNP (p<0.001) relative to CON during ischemia. Despite differences in baroreceptor loading status, no difference in LSR or CVC were observed under NS and MHS. However, during HHS, LBNP significantly reduced CVC by 16% (p=0.028) and LSR by 7% (p=0.036) relative to CON. In contrast, LBPP significantly elevated CVC by 23% relative to CON (p=0.013), albeit no differences in LSR were observed (p=0.909). These data suggest that baroreceptor loading status can modulate metaboreceptor-mediated changes in local heat loss responses but only under elevated levels of thermal stress (Tes ≥ 1.2°C). Support: Natural Sciences and Engineering Research Council (Dr. G. Kenny)

Turning the PAGe on central control of the exercise pressor reflex in humans

experiments in biological science are often envisioned as ultimately providing rational approaches to problems confronting human health. Additionally, pragmatic solutions evoked by clinical problems often provoke new questions in basic science. Deep brain stimulation therapy in human patients with

Forearm vascular responses to combined muscle metaboreceptor activation in the upper and lower limbs in humans

Our previous studies showed that venous occlusion or passive stretch of the lower limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non-exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb. In this study, we investigated whether a metabolic stimulus to the lower limb induces a similar response. Eight subjects performed a 2 min static handgrip exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30% MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non-exercised arm decreased significantly, whereas during combined PEMI of the upper and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb was attenuated. Forearm blood flow and FVC were significantly greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. When PEMI of the lower limb was released after combined PEMI of the upper and lower limbs (only PEMI of the upper limb was maintained continuously), the attenuated decreases in FBF and FVC observed during combined PEMI of the upper and lower limbs was not observed. Thus, forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs.

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.

Passive triceps surae stretch inhibits vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated whether selective muscle mechanoreceptor activation in the lower limb opposes arm muscle metaboreceptor activation-mediated limb vasoconstriction. Seven subjects completed two trials: one control trial and one stretch trial. Both trials included 2 min of handgrip and 2 min of posthandgrip exercise muscle ischemia (PEMI). In the stretch trial, a 2-min sustained triceps surae stretch, by brief passive dorsiflexion of the right foot, was performed simultaneously during PEMI. Mean arterial pressure, heart rate, and forearm blood flow (FBF) in the nonexercised arm and forearm vascular conductance (FVC) in the nonexercised arm were measured. During PEMI in the control trial, mean arterial pressure was significantly greater and FBF and FVC were significantly lower than baseline values (P < 0.05 for each). In contrast, FBF and FVC during PEMI in the stretch trial exhibited different responses than in the control trial. FBF and FVC were significantly greater in the stretch trial than in the control trial (FBF, 5.5 +/- 0.4 vs. 3.8 +/- 0.4 ml x 100 ml(-1) x min(-1); FVC, 0.048 +/- 0.004 vs. 0.033 +/- 0.003 unit, respectively; P < 0.05). These results indicate that passive triceps surae stretch can inhibit vasoconstriction in the nonexercised forearm mediated via muscle metaboreceptor activation in the exercised arm.

Peripheral muscle ergoreceptors and ventilatory response during exercise recovery in heart failure.

Recent studies have suggested that the increased ventilatory response during exercise in patients with chronic heart failure was related to the activation of muscle metaboreceptors. To address this issue, 23 patients with heart failure and 7 normal subjects performed arm and leg bicycle exercises with and without cuff inflation around the arms or the thighs during recovery. Obstruction slightly reduced ventilation and gas exchange variables at recovery but did not change the kinetics of recovery of these parameters compared with nonobstructed recovery: half-time of ventilation recovery was 175 +/- 54 to 176 +/- 40 s in patients and 155 +/- 66 to 127 +/- 13 s in controls (P < 0.05, patients vs. controls, not significant within each group from baseline to obstructed recovery). We conclude that muscle metaboreceptor activation does not seem to play a role in the exertion hyperventilation of patients with heart failure.

Neural processes in thermoregulation.

Neural processes in thermoregulation.

Importance of skin temperature in the regulation of sweating.

Human sweating regulation at rest, evaluating thermal inputs effects on thermoregulatory center and internal hypothalamic and skin temperatures

Partitional calorimetric studies of responses of man to thermal transients.

Partitional calorimetric studies of responses of man to thermal transients.