Blockade of endogenous insulin receptor signaling in the nucleus tractus solitarius potentiates exercise pressor reflex function in healthy male rats.

Insulin not only regulates glucose and/or lipid metabolism but also modulates brain neural activity. The nucleus tractus solitarius (NTS) is a key central integration site for sensory input from working skeletal muscle and arterial baroreceptors during exercise. Stimulation of the skeletal muscle exercise pressor reflex (EPR), the responses of which are buffered by the arterial baroreflex, leads to compensatory increases in arterial pressure to supply blood to working muscle. Evidence suggests that insulin signaling decreases neuronal excitability in the brain, thus antagonizing insulin receptors (IRs) may increase neuronal excitability. However, the impact of brain insulin signaling on the EPR remains fully undetermined. We hypothesized that antagonism of NTS IRs increases EPR function in normal healthy rodents. In decerebrate rats, stimulation of the EPR via electrically induced muscle contractions increased peak mean arterial pressure (MAP) responses 30 min following NTS microinjections of an IR antagonist (GSK1838705, 100 µM; Pre: Δ16 ± 10 mmHg vs. 30 min: Δ23 ± 13 mmHg, n = 11, p = .004), a finding absent in sino-aortic baroreceptor denervated rats. Intrathecal injections of GSK1838705 did not influence peak MAP responses to mechano- or chemoreflex stimulation of the hindlimb muscle. Immunofluorescence triple overlap analysis following repetitive EPR stimulation increased c-Fos overlap with EPR-sensitive nuclei and IR-positive cells relative to sham operation (p < .001). The results suggest that IR blockade in the NTS potentiates the MAP response to EPR stimulation. In addition, insulin signaling in the NTS may buffer EPR stimulated increases in blood pressure via baroreflex-mediated mechanisms during exercise.

Antagonism of TRPV4 channels partially reduces mechanotransduction in rat skeletal muscle afferents.

Mechanical distortion of working skeletal muscle induces sympathoexcitation via thin fibre afferents, a reflex response known as the skeletal muscle mechanoreflex. However, to date, the receptor ion channels responsible for mechanotransduction in skeletal muscle remain largely undetermined. Transient receptor potential vanilloid 4 (TRPV4) is known to sense mechanical stimuli such as shear stress or osmotic pressure in various organs. It is hypothesized that TRPV4 in thin-fibre primary afferents innervating skeletal muscle is involved in mechanotransduction. Fluorescence immunostaining revealed that 20.1 ± 10.1% of TRPV4 positive neurons were small dorsal root ganglion (DRG) neurons that were DiI-labelled, and among them 9.5 ± 6.1% of TRPV4 co-localized with the C-fibre marker peripherin. In vitro whole-cell patch clamp recordings from cultured rat DRG neurons demonstrated that mechanically activated current amplitude was significantly attenuated after the application of the TRPV4 antagonist HC067047 compared to control (P = 0.004). Such reductions were also observed in single-fibre recordings from a muscle-nerve ex vivo preparation where HC067047 significantly decreased afferent discharge to mechanical stimulation (P = 0.007). Likewise, in an in vivo decerebrate rat preparation, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to passive stretch of hindlimb muscle were significantly reduced by intra-arterial injection of HC067047 (ΔRSNA: P = 0.019, ΔMAP: P = 0.002). The findings suggest that TRPV4 plays an important role in mechanotransduction contributing to the cardiovascular responses evoked by the skeletal muscle mechanoreflex during exercise. KEY POINTS: Although a mechanical stimulus to skeletal muscle reflexively activates the sympathetic nervous system, the receptors responsible for mechanotransduction in skeletal muscle thin fibre afferents have not been fully identified. Evidence suggests that TRPV4 is a mechanosensitive channel that plays an important role in mechanotransduction within various organs. Immunocytochemical staining demonstrates that TRPV4 is expressed in group IV skeletal muscle afferents. In addition, we show that the TRPV4 antagonist HC067047 decreases the responsiveness of thin fibre afferents to mechanical stimulation at the muscle tissue level as well as at the level of dorsal root ganglion neurons. Moreover, we demonstrate that intra-arterial HC067047 injection attenuates the sympathetic and pressor responses to passive muscle stretch in decerebrate rats. These data suggest that antagonism of TRPV4 attenuates mechanotransduction in skeletal muscle afferents. The present study demonstrates a probable physiological role for TRPV4 in the regulation of mechanical sensation in somatosensory thin fibre muscle afferents.

Neural discharge of muscle afferents and pressor response to mechanical stimulation are associated with muscle deformation velocity in rats.

Skeletal muscle reflexes play a crucial role in determining the magnitude of the cardiovascular response to exercise. However, evidence supporting an association between the magnitude of the pressor response and the velocity of muscle deformation has remained to be elucidated. Thus, we investigated the impact of different muscle deformation rates on the neural discharge of muscle afferents and pressor and sympathetic responses in Sprague-Dawley rats. In an ex vivo muscle-nerve preparation, action potentials elicited by sinusoidal mechanical stimuli (137 mN) at different frequencies (0.01, 0.05, 0.1, 0.2, and 0.25 Hz) were recorded in mechanosensitive group III and IV fibers. The afferent response magnitude to sine-wave stimulation significantly varied at different frequencies (ANOVA, P = 0.01). Specifically, as compared with 0.01 Hz (0.83 ± 0.96 spikes/s), the response magnitudes were significantly greater at 0.20 Hz (4.07 ± 5.04 spikes/s, P = 0.031) and 0.25 Hz (4.91 ± 5.30 spikes/s, P = 0.014). In an in vivo decerebrated rat preparation, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to passive stretch (1 kg) of hindlimb skeletal muscle at different velocities of loading (slow, medium, and fast) were measured. Pressor responses to passive stretch were significantly associated with the velocity of muscle deformation (ANOVA, P < 0.001). The MAP response to fast stretch (Δ 56 ± 12 mmHg) was greater than slow (Δ 33 ± 11 mmHg, P = 0.006) or medium (Δ 30 ± 11 mmHg, P < 0.001) stretch. Likewise, the RSNA response was related to deformation velocity (ANOVA, P = 0.024). These findings suggest that the muscle neural afferent discharge and the cardiovascular response to mechanical stimulation are associated with muscle deformation velocity.

Insulin potentiates the response to capsaicin in dorsal root ganglion neurons in vitro and muscle afferents ex vivo in normal healthy rodents.

Systemic insulin administration evokes sympathoexcitatory actions, but the mechanisms underlying these observations are unknown. We reported that insulin sensitizes the response of thin-fibre primary afferents, as well as the dorsal root ganglion (DRG) that subserves them, to mechanical stimuli. However, little is known about the effects of insulin on primary neuronal responses to chemical stimuli. TRPV1, whose agonist is capsaicin (CAP), is widely expressed on chemically sensitive metaboreceptors and/or nociceptors. The aim of this investigation was to determine the effects of insulin on CAP-activated currents in small DRG neurons and CAP-induced action potentials in thin-fibre muscle afferents of normal healthy rodents. Additionally, we investigated whether insulin potentiates sympathetic nerve activity (SNA) responses to CAP. In whole-cell patch-clamp recordings from cultured mice DRG neurons in vitro, the fold change in CAP-activated current from pre- to post-application of insulin (n = 13) was significantly (P < 0.05) higher than with a vehicle control (n = 14). Similar results were observed in single-fibre recording experiments ex vivo as insulin potentiated CAP-induced action potentials compared to vehicle controls (n = 9 per group, P < 0.05). Furthermore, insulin receptor blockade with GSK1838705 significantly suppressed the insulin-induced augmentation in CAP-activated currents (n = 13) as well as the response magnitude of CAP-induced action potentials (n = 9). Likewise, the renal SNA response to CAP after intramuscular injection of insulin (n = 8) was significantly (P < 0.05) greater compared to vehicle (n = 9). The findings suggest that insulin potentiates TRPV1 responsiveness to CAP at the DRG and muscle tissue levels, possibly contributing to the augmentation in sympathoexcitation during activities such as physical exercise. KEY POINTS: Evidence suggests insulin centrally activates the sympathetic nervous system, and a chemical stimulus to tissues activates the sympathetic nervous system via thin fibre muscle afferents. Insulin is reported to modulate putative chemical-sensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, it is demonstrated that insulin potentiates the responsiveness of thin fibre afferents to capsaicin at muscle tissue levels as well as at the level of dorsal root ganglion neurons. In addition, it is demonstrated that insulin augments the sympathetic nerve activity response to capsaicin in vivo. These data suggest that sympathoexcitation is peripherally mediated via insulin-induced chemical sensitization. The present study proposes a possible physiological role of insulin in the regulation of chemical sensitivity in somatosensory thin fibre muscle afferents.

The effectiveness of bench step exercise for ameliorating acute mental stress-induced arterial stiffening.

PURPOSE: This study aimed to evaluate the effectiveness of bench step (BS) exercise for ameliorating arterial stiffening caused by acute mental stress (MS). METHODS: Fifteen young healthy men participated in two randomized trials: rest (RE) and exercise (EX) trials. Following a 5-min MS task (first task), the RE trial participants rested on a chair for 10 min (from 10 to 20 min after task cessation); the EX trial participants performed BS exercise for the same duration. At 40 min after the first task, the participants performed the same task (second task) again. Heart-brachial pulse wave velocity (PWV) (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and the cardio-ankle vascular index (CAVI) were measured simultaneously at 5, 30, and 50 min after the first task. RESULTS: Both trials caused significant elevations in hbPWV, haPWV, and CAVI at 5 min after the first task; these changes persisted until 30 min after the task in the RE trial, while they were abolished in the EX trial. baPWV significantly increased at 30 min after the task in the RE trial, but not in the EX trial. After the second task (from 30 to 50 min after the first task), none of the parameters significantly increased in the RE trial, although the values remained above baseline levels. In the EX trial, hbPWV, haPWV, and CAVI showed significant elevations. CONCLUSION: Our findings suggest that a 10-min BS exercise after acute MS can counteract stress-induced arterial stiffening, but has only a limited effect against subsequent acute MS.

The Impact of Insulin Resistance on Cardiovascular Control During Exercise in Diabetes.

Patients with diabetes display heightened blood pressure response to exercise, but the underlying mechanism remains to be elucidated. There is no direct evidence that insulin resistance (hyperinsulinemia or hyperglycemia) impacts neural cardiovascular control during exercise. We propose a novel paradigm in which hyperinsulinemia or hyperglycemia significantly influences neural regulatory pathways controlling the circulation during exercise in diabetes.

Acute mental stress-caused arterial stiffening can be counteracted by brief aerobic exercise.

PURPOSE: Acute mental stress (MS) causes an elevation in pulse wave velocity (PWV), an index of arterial stiffness. In contrast, aerobic exercise acutely decreases arterial stiffness, even in the short term. The present study aimed to examine whether acute MS-caused arterial stiffening can be counteracted by brief aerobic exercise. METHODS: Thirteen young healthy men (mean age, 20 ± 1 years) participated in two randomized experimental visits where they were subjected to acute MS followed by seated rest (RE) or cycling exercise (EX) trials. Following a 5-min MS task, the participants in the RE trial rested on a chair for 10 min (from 10 to 20 min after the cessation of the task), whereas those in the EX trial cycled at 35% of heart rate reserve for the same duration. Heart-brachial PWV (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and the cardio-ankle vascular index (CAVI) were simultaneously measured at baseline and 5, 30, and 45 min after the task. RESULTS: Both trials caused significant elevations (P < 0.05) in hbPWV, haPWV, and CAVI at 5 min after the task; subsequently, this persisted until 45 min after the task in the RE trial, whereas the elevations in the EX trial were eliminated. In the RE trial, baPWV significantly increased (P < 0.05) at 30 and 45 min after the task, whereas such an increase was not observed in the EX trial. CONCLUSION: The findings of the present study reveal that brief aerobic exercise counteracts arterial stiffening caused by acute MS.

Impact of acute mental stress on segmental arterial stiffness.

PURPOSE: It has been reported that acute brief episodes of mental stress (MS) result in a prolonged increase in carotid-femoral pulse wave velocity (cfPWV), an index of aortic stiffness. However, whether acute MS also impacts arterial stiffness in other segments is unclear. The present study aimed to examine the impact of acute MS on segmental arterial stiffness. METHODS: In the main experiment, 17 young male subjects (mean age, 20.1 ± 0.7 years) performed a 5-min MS and control (CON) task in a random order. Pulse wave velocity (PWV) from the heart to the brachium (hbPWV) and the ankle (haPWV), PWV between the brachial artery and the ankle (baPWV), and the cardio-ankle vascular index (CAVI) were simultaneously measured at baseline and 5, 15, and 30 min after the task. RESULTS: Compared to baseline values, hbPWV, baPWV, haPWV, and CAVI significantly increased until 30 min after the MS task, whereas these variables did not significantly change following the CON task. At 5 and 30 min after the MS task, percentage changes from baseline were significantly higher in hbPWV (+ 5.2 ± 4.4 and 6.6 ± 4.9%) than in baPWV (+ 2.2 ± 2.1 and 2.2 ± 2.0%) or haPWV (+ 3.6 ± 2.6 and 4.3 ± 2.9%) and were also significantly lower in baPWV than in haPWV. CONCLUSION: These findings suggest that acute MS elicits an increase in arterial stiffness in various segments and this arterial stiffening is not uniform among the segments.

Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro.

KEY POINTS: Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin-induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents. ABSTRACT: Insulin activates the sympathetic nervous system, although the mechanism underlying insulin-induced sympathoexcitation remains to be determined. A mechanical stimulus to tissues such as skin and/or skeletal muscle, no matter whether the stimulation is noxious or not, activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion (DRG) neurons of these afferents. Accordingly, we investigated whether insulin augments whole-cell current responses to mechanical stimuli in small DRG neurons of normal healthy mice. We performed whole-cell patch clamp recordings using cultured DRG neurons and observed mechanically-activated (MA) currents induced by mechanical stimuli applied to the cell surface. Local application of vehicle solution did not change MA currents or mechanical threshold in cultured DRG neurons. Insulin (500 mU mL-1 ) significantly augmented the amplitude of MA currents (P < 0.05) and decreased the mechanical threshold (P < 0.05). Importantly, pretreatment with the insulin receptor antagonist, GSK1838705, significantly suppressed the insulin-induced potentiation of the mechanical response. We further examined the impact of insulin on thin fibre muscle afferent activity in response to mechanical stimuli in normal healthy rats in vitro. Using a muscle-nerve preparation, we recorded single group IV fibre activity to a ramp-shaped mechanical stimulation. Insulin significantly decreased mechanical threshold (P < 0.05), although it did not significantly increase the response magnitude to the mechanical stimulus. In conclusion, these data suggest that insulin augments the mechanical responsiveness of small DRG neurons and potentially sensitizes group IV afferents to mechanical stimuli at the muscle tissue level, possibly contributing to insulin-induced sympathoexcitation.

Exaggerated pressor and sympathetic responses to stimulation of the mesencephalic locomotor region and exercise pressor reflex in type 2 diabetic rats.

The cardiovascular responses to exercise are potentiated in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms causing this abnormality remain unknown. Central command (CC) and the exercise pressor reflex (EPR) are known to contribute significantly to cardiovascular control during exercise. Thus these neural signals are viable candidates for the generation of the abnormal circulatory regulation in this disease. We hypothesized that augmentations in CC as well as EPR function contribute to the heightened cardiovascular responses during exercise in T2DM. To test this hypothesis, changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to electrical stimulation of mesencephalic locomotor region (MLR), a putative component of the central command pathway, and activation of the EPR, evoked by electrically induced hindlimb muscle contraction, were examined in decerebrate animals. Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet (14-16 wk) in combination with two low doses (35 mg/kg week 1, 25 mg/kg week 2) of streptozotocin (T2DM). The changes in MAP and RSNA responses to MLR stimulation were significantly greater in T2DM compared with control (2,739 ± 123 vs. 1,298 ± 371 mmHg/s, 6,326 ± 1,621 vs. 1,390 ± 277%/s, respectively, P < 0.05). Similarly, pressor and sympathetic responses to activation of the EPR in diabetic animals were significantly augmented compared with control animals (436 ± 74 vs. 134 ± 44 mmHg/s, 645 ± 135 vs. 139 ± 65%/s, respectively, P < 0.05). These findings provide the first evidence that CC and the EPR may generate the exaggerated rise in sympathetic activity and blood pressure during exercise in T2DM.

Mechanosensitive channels in the mechanical component of the exercise pressor reflex.

The cardiovascular response is appropriately regulated during exercise to meet the metabolic demands of the active muscles. The exercise pressor reflex is a neural feedback mechanism through thin-fiber muscle afferents activated by mechanical and metabolic stimuli in the active skeletal muscles. The mechanical component of this reflex is referred to as skeletal muscle mechanoreflex. Its initial step requires mechanotransduction mediated by mechanosensors, which convert mechanical stimuli into biological signals. Recently, various mechanosensors have been identified, and their contributions to muscle mechanoreflex have been actively investigated. Nevertheless, the mechanosensitive channels responsible for this muscular reflex remain largely unknown. This review discusses progress in our understanding of muscle mechanoreflex under healthy conditions, focusing on mechanosensitive channels.

Vacuolar-ATPase-mediated muscle acidification caused muscular mechanical nociceptive hypersensitivity after chronic stress in rats, which involved extracellular matrix proteoglycan and ASIC3.

Although widespread pain, such as fibromyalgia, is considered to have a central cause, peripheral input is important. We used a rat repeated cold stress (RCS) model with many characteristics common to fibromyalgia and studied the possible involvement of decreased muscle pH in muscle mechanical hyperalgesia. After a 5-day RCS, the muscle pH and the muscular mechanical withdrawal threshold (MMWT) decreased significantly. Subcutaneously injected specific inhibitor of vacuolar ATPase (V-ATPase), bafilomycin A1, reversed both changes almost completely. It also reversed the increased mechanical response of muscle thin-fibre afferents after RCS. These results show that V-ATPase activation caused muscle pH drop, which led to mechanical hypersensitivity after RCS. Since extracellular matrix proteoglycan and acid sensitive ion channels (TRPV1 and ASIC3) have been considered as possible mechanisms for sensitizing/activating nociceptors by protons, we investigated their involvement. Manipulating the extracellular matrix proteoglycan with chondroitin sulfate and chondroitinase ABC reversed the MMWT decrease after RCS, supporting the involvement of the extracellular mechanism. Inhibiting ASIC3, but not TRPV1, reversed the decreased MMWT after RCS, and ASIC3 mRNA and protein in the dorsal root ganglia were upregulated, indicating ASIC3 involvement. These findings suggest that extracellular mechanism and ASIC3 play essential roles in proton-induced mechanical hyperalgesia after RCS.

Three-minute bench step exercise as a countermeasure for acute mental stress-induced arterial stiffening.

Acute mental stress (MS) induces a transient increase in arterial stiffness. We verified whether a single bout of bench step (BS) exercise for 3 minutes counteracts acute MS-induced arterial stiffening. Fifteen healthy young men (mean age, 21.7 ± 0.3 years) underwent two experimental trials: rest (RE) and exercise (EX) trials. Following a 5-minute MS task, the participants in the RE trial rested on a chair for 3 minutes (from 10 to 13 minutes after task cessation), whereas those in the EX trial performed the BS exercise for the same duration. The heart-brachial pulse wave velocity (PWV) (hbPWV), brachial-ankle PWV (baPWV), heart-ankle PWV (haPWV), and the cardio-ankle vascular index (CAVI) were measured at baseline and at 5 and 30 minutes after the task. In both trials, significant increases in hbPWV, haPWV, and CAVI occurred at 5 minutes after the task; these elevations persisted until 30 minutes after the task in the RE trial, but significantly decreased to baseline levels in the EX trial. baPWV was significantly elevated at 30 minutes after the task in the RE trial, but not in the EX trial. This study reveals that a 3-minute BS exercise offsets acute MS-induced arterial stiffening.

Impact of acute mental stress on ankle blood pressure in young healthy men: a pilot study.

OBJECTIVE: Acute mental stress (MS) increases arm blood pressure (BP); however, it remains unclear whether a stress-induced pressor response is also observed in other vessels. This study aimed to examine the impact of acute MS on ankle BP. Fifty-six young, healthy men aged 19-24 years were divided into the MS (n = 29) and control (CON) (n = 27) groups; each group performed 5-min MS (mental arithmetic) or CON tasks. Systolic and diastolic BPs (SBP and DBP, respectively) of both the brachial and posterior tibial arteries were simultaneously measured at the baseline and 5 and 30 min after the task. RESULTS: In the MS group, brachial BP measures significantly increased (P < 0.05) until 30 min after the task; ankle BP measures were also significantly (P < 0.05) elevated during this time. In the CON group, no significant changes were found in brachial BP measures or ankle SBP, whereas a significant increase (P < 0.05) in ankle DBP was observed 30 min after the task. Our findings indicate that both brachial and ankle BP exhibit a sustained elevation after acute MS, suggesting a systemic pressor response by stress exposure. The measurement of ankle BP in addition to arm BP may be important to assess the stress response. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000047796 Registered on: 20th May 2022.

Blood flow restriction accelerates aerobic training-induced adaptation of [Formula: see text] kinetics at the onset of moderate-intensity exercise.

It is unclear whether blood flow restriction (BFR) accelerates the adaptation of the time constant (τ) of phase II oxygen uptake ([Formula: see text]) kinetics in the moderate-intensity exercise domain via moderate-intensity aerobic training. Therefore, healthy participants underwent moderate-intensity [45-60% [Formula: see text] Reserve] aerobic cycle training with or without BFR (BFR group, n = 9; CON group, n = 9) for 8 weeks to evaluate [Formula: see text] kinetics during moderate-intensity cycle exercise before (Pre) and after 4 (Mid) and 8 (Post) weeks of training. Both groups trained for 30 min, 3 days weekly. BFR was performed for 5 min every 10 min by applying cuffs to the upper thighs. The τ significantly decreased by Mid in the BFR group (23.7 ± 2.9 s [Pre], 15.3 ± 1.8 s [Mid], 15.5 ± 1.4 s [Post], P < 0.01) and by Post in the CON group (27.5 ± 2.0 s [Pre], 22.1 ± 0.7 s [Mid], 18.5 ± 1.9 s [Post], P < 0.01). Notably, the BFR group's τ was significantly lower than that of the CON group at Mid (P < 0.01) but not at Post. In conclusion, BFR accelerates the adaptation of the [Formula: see text] kinetics of phase II by moderate-intensity aerobic training.

Exaggerated pressor response to blood flow restriction resistance exercise is associated with a muscle metaboreflex-induced increase in blood pressure in young, healthy humans.

Some researchers are concerned that exercise training with the blood flow restriction (BFR) technique induces an exaggeration in blood pressure response and potentiates adverse cardiovascular events. In the present study, we demonstrate that the blood pressure response to arm-curl exercise was intensified by the BFR technique, and the degree of intensification was associated with a blood pressure response to postexercise muscle ischemia of the elbow flexors, which elicit a muscle metaboreflex. Novelty: BFR technique intensifies blood pressure response to exercise, which was associated with a blood pressure response in postexercise muscle ischemia-induced muscle metaboreflex.

Aging exaggerates blood pressure response to ischemic rhythmic handgrip exercise in humans.

Ischemic skeletal muscle conditions are known to augment exercise-induced increases in blood pressure (BP). Aging is also a factor that enhances the pressor response to exercise. However, the effects of aging on the BP response to ischemic exercise remain unclear. We, therefore, tested the hypothesis that aging enhances the BP response to rhythmic handgrip (RHG) exercise during postexercise muscle ischemia (PEMI). We divided the normotensive participants without cardiovascular diseases into three age groups: young (n = 26; age, 18-28 years), middle-aged (n = 23; age, 35-59 years), and older adults (n = 23; age, 60-80 years). The participants performed RHG exercise with minimal effort for 1 min after rest with and without PEMI, which was induced by inflating a cuff on the upper arm just before the isometric handgrip exercise ended; the intensity was 30% of maximal voluntary contraction force. Under PEMI, the increase in diastolic BP (DBP) from rest to RHG exercise in the older adult group (Δ13 ± 2 mmHg) was significantly higher than that in the young (Δ5 ± 2 mmHg) and middle-aged groups (Δ6 ± 1 mmHg), despite there being no significant difference between the groups in the DBP response from rest to RHG exercise without PEMI. Importantly, based on multiple regression analysis, age remained a significant independent determinant of both the SBP and DBP responses to RHG exercise during PEMI (p < 0.01). These findings indicate that aging enhances the pressor response to ischemic rhythmic exercise.

TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia.

[Figure: see text].

Low pH enhances response of thin muscle afferents to mechanical stimuli.

We examined whether acidic buffer sensitizes thin muscular afferents to mechanical stimulus using single-fiber recording. The EDL muscle with the common peroneal nerve attached was excised from 17-male SD rats under pentobarbital anesthesia. After identifying single thin afferent fibers, mechanical stimulus was applied to their receptive fields using a servo-controlled mechanical stimulator before and after pH 6.2-solution was applied to the receptive field. The effect of pH 7.4-solution was similarly examined as a control. Application of pH 7.4-solution did not induce any change in the mechanical threshold or increase in the number of discharges evoked during stimulation over the number of spontaneous discharges (response magnitude). However, pH 6.2-solution significantly lowered the mechanical threshold and increased the response magnitude, suggesting that the mechanical sensitivity of thin muscle afferents was augmented by exposure to acidic pH, which is seen during exercise. This change could be involved in respiratory control during exercise.

Aerobic exercise capacity and muscle volume after lower limb suspension with exercise countermeasure.

INTRODUCTION: The purpose of the present study was to elucidate the effect of unilateral lower limb suspension (ULLS) on aerobic capacity during one-legged cycle exercise and whether the change in aerobic exercise capacity after ULLS with or without intensive interval training is related to the change in skeletal muscle volume. METHODS: There were 13 young men who underwent 20 d of ULLS and were divided into 2 groups based on some physical characteristics: the control group (CON; N=7) and the trained group (TRN; N=6). Subjects in TRN underwent interval cycle training on alternate days during ULLS. The respiratory and circulatory responses to one-legged incremental cycling and muscle volume of the thigh were measured before and after 20 d of ULLS. RESULTS: : One-legged peak oxygen uptake (VO2peak) and total muscle volume of the thigh in CON decreased significantly after 20 d of ULLS (-11.0 +/- 3.5% in VO2peak, -6.1 +/- 1.8% in total muscle volume). However, these parameters were maintained in TRN (+0.2 +/- 5.2% in VO2peaka, -1.0 +/- 1.8% in total muscle volume). Circulatory variables at rest and during submaximal exercise were unchanged in both groups after ULLS. Changes in one-legged VO2peak were significantly correlated with change in total muscle volume of the thigh in CON. CONCLUSION: Our findings indicated that peripheral adaptations after ULLS could relate to the change in aerobic exercise capacity during one-legged exercise. Our results also suggest that intensive interval training prevents ULLS-induced deconditioning of both aerobic exercise capacity and skeletal muscle volume.