Activation of Mechanoreflex, but not Central Command, Delays Heart Rate Recovery after Exercise in Healthy Men

This study tested the hypotheses that activation of central command and muscle mechanoreflex during post-exercise recovery delays fast-phase heart rate recovery with little influence on the slow phase. Twenty-five healthy men underwent three submaximal cycling bouts, each followed by a different 5-min recovery protocol: active (cycling generated by the own subject), passive (cycling generated by external force) and inactive (no-cycling). Heart rate recovery was assessed by the heart rate decay from peak exercise to 30 s and 60 s of recovery (HRR30s, HRR60s fast phase) and from 60 s-to-300 s of recovery (HRR60−300s slow phase). The effect of central command was examined by comparing active and passive recoveries (with and without central command activation) and the effect of mechanoreflex was assessed by comparing passive and inactive recoveries (with and without mechanoreflex activation). Heart rate recovery was similar between active and passive recoveries, regardless of the phase. Heart rate recovery was slower in the passive than inactive recovery in the fast phase (HRR60s=20±8vs.27 ±10 bpm, p<0.01), but not in the slow phase (HRR60−300s=13±8vs.10±8 bpm, p=0.11). In conclusion, activation of mechanoreflex, but not central command, during recovery delays fast-phase heart rate recovery. These results elucidate important neural mechanisms behind heart rate recovery regulation.

Passive bilateral leg cycling with concomitant regional circulatory occlusion for testing mechanoreflex–metaboreflex interactions in humans

Purpose The exercise pressor reflex (EPR) plays a fundamental role in physiological reactions to exercise in humans and in the pathophysiology of cardiovascular disorders. There is no “gold standard” method for EPR assessment; therefore, we propose a new protocol for testing interactions between the muscle mechanoreflex and metaboreflex (major components of EPR). Methods Thirty-four healthy subjects (mean age [± standard deviation] 24 ± 4 years, 22 men) were enrolled in the study. During the study, the hemodynamic and ventilatory parameters of these subjects were continuously monitored using our proposed assessment method. This assessment method consists of an initial 5-min rest period (baseline) followed by 5 min of passive cycling (PC) on an automated cycle ergometer (mechanoreceptor stimulation), after which tourniquet cuffs located bilaterally on the upper thighs are inflated for 3 min to evoke venous and arterial regional circulatory occlusion (CO) during PC (metaboreceptor stimulation). Deflation of the tourniquet cuffs is followed by a second 5 min of PC and finally by a 5-min recovery time. The control test comprises a 5-min rest period, followed by 3 min of CO only and a final 5-min recovery. Results Mean arterial pressure (MAP) and minute ventilation (MV) increased significantly during PC (MAP: from 90 ± 9.3 to 95 ± 9.7 mmHg; MV: from 11.5 ± 2.5 to 13.5 ± 2.9 L/min; both p < 0.05) and again when CO was applied (MAP: from 95 ± 9.7 to 101 ± 11.0 mmHg; MV: from 13.5 ± 2.9 to 14.8 ± 3.8 L/min; both p < 0.05). In the control test there was a slight increase in MAP during CO (from 92 ± 10.5 to 94 ± 10.0 mmHg; p < 0.05) and no changes in the ventilatory parameters. Conclusion Bilateral leg passive cycling with concomitant circulatory occlusion is a new, simple and effective method for testing interactions between the mechanoreflex and metaboreflex in humans.

Thromboxane A2 receptors mediate chronic mechanoreflex sensitization in a rat model of simulated peripheral artery disease

We demonstrate that thromboxane A2 receptors, but not endoperoxide 4 receptors, on the sensory endings of thin fiber muscle afferents contribute to the chronic sensitization of the muscle mechanoreflex in rats with a ligated femoral artery (a model of simulated peripheral artery disease). The data may have important implications for our understanding of blood pressure control during exercise in patients with peripheral artery disease.

Metabolic acidosis augments exercise pressor responses in chronic kidney disease

Chronic kidney disease (CKD) patients experience augmented blood pressure (BP) reactivity during exercise that is associated with an increased risk of cardiovascular mortality. Exaggerated exercise pressor responses in CKD are in part mediated by augmented sympathetic nerve activation due to heightened muscle mechanoreflex. One mechanism that may lead to sensitization of the muscle mechanoreflex in CKD is metabolic acidosis. We hypothesized that CKD patients with low serum [bicarbonate] would exhibit exaggerated increases in arterial BP, greater reductions in muscle interstitial pH, and fatigue earlier during exercise compared with CKD patients with normal serum bicarbonate concentration ([bicarbonate]). Eighteen CKD participants with normal serum [bicarbonate] (≥24 mmol/l, normal-bicarb) and 9 CKD participants with mild metabolic acidosis ([bicarbonate] range 20–22 mmol/l, low-bicarb) performed rhythmic handgrip (RHG) exercise to volitional fatigue at 40% of maximal voluntary contraction. BP, heart rate, and muscle interstitial pH using near infrared spectroscopy were measured continuously. While mean arterial pressure (MAP) increased with exercise in both groups ( P ≤ 0.002), CKD with low-bicarb had an exaggerated MAP response compared with CKD with normal-bicarb (+5.9 ± 1.3 mmHg/30 s vs. +2.6 ± 0.5 mmHg/30 s, P = 0.01). The low-bicarb group reached exhaustion earlier than the normal-bicarb group (179 ± 21 vs. 279 ± 19 s, P = 0.003). There were no differences in the change in muscle interstitial pH during exercise between groups ( P = 0.31). CKD patients with metabolic acidosis have augmented exercise-induced increases in BP and poorer exercise tolerance. There was no difference in change in muscle interstitial pH between groups, however, suggesting that augmented exercise BP responses in metabolic acidosis are not due to impaired muscle-buffering capacity.

Chondroitin sulfate attenuates acid-induced augmentation of the mechanical response in rat thin-fiber muscle afferents in vitro

Exercise-induced tissue acidosis augments the exercise pressor reflex (EPR). One reason for this may be acid-induced mechanical sensitization in thin-fiber muscle afferents, which is presumably related to EPR. Acid-induced sensitization to mechanical stimulation has been reported to be attenuated in cultured primary-sensory neurons by exogenous chondroitin sulfate (CS) and chondroitinase ABC, suggesting that the extracellular matrix CS proteoglycan is involved in this sensitization. The purpose of this study was to clarify whether acid-induced sensitization of the mechanical response in the thin-fiber muscle afferents is also suppressed by exogenous CS and chondroitinase ABC using a single-fiber recording technique. A total of 88 thin fibers (conduction velocity <15.0 m/s) dissected from 86 male Sprague-Dawley rats were identified. A buffer solution at pH 6.2 lowered their mechanical threshold and increased their response magnitude. Five minutes after CS (0.3 and 0.03%) injection near the receptive field, these acid-induced changes were significantly reduced. No significant difference in attenuation was detected between the two CS concentrations. Chondroitinase ABC also significantly attenuated this sensitization. The control solution (0% CS) did not significantly alter the mechanical sensitization. Furthermore, no significant differences were detected in this sensitization and CS-based suppression between fibers with and without acid-sensitive channels [transient receptor potential vanilloid 1 (TRPV1), acid-sensing ion channel (ASIC)]. In addition, this mechanical sensitization was not changed by TRPV1 and ASIC antagonists, suggesting that these ion channels are not involved in the acid-induced mechanical sensitization of muscle thin-fiber afferents. In conclusion, CS administration has a potential to attenuate the acidosis-induced exaggeration of muscle mechanoreflex. NEW & NOTEWORTHY We found that exogenous chondroitin sulfate attenuated acid-induced mechanical sensitization in thin-fiber muscle afferents that play a crucial role in the exercise pressor reflex. This finding suggests that extracellular matrix chondroitin sulfate proteoglycans may be involved in the mechanism of acid-induced mechanical sensitization and that daily intake of chondroitin sulfate may potentially attenuate this amplification of muscle mechanoreflex and therefore reduce muscle pain related to acidic muscle conditions.