Tidal expiratory flow limitation during exercise is unrelated to peripheral hypercapnic chemosensitivity.

We sought to determine if peripheral hypercapnic chemosensitivity is related to expiratory flow limitation (EFL) during exercise. Twenty participants completed one testing day which consisted of peripheral hypercapnic chemosensitivity testing and a maximal exercise test to exhaustion. The chemosensitivity testing consisting of two breaths of 10% CO2 (O2∼21%) repeated 5 times during seated rest and the first 2 exercise intensities during the maximal exercise test. Following chemosensitivity testing, participants continued cycling with the intensity increasing 20 W every 1.5 minutes till exhaustion. Maximal expiratory flow-volume curves were derived from forced expiratory capacity maneuvers performed before and after exercise at varying efforts. Inspiratory capacity maneuvers were performed during each exercise stage to determine EFL. There was no difference between the EFL and non-EFL hypercapnic chemoresponse (mean response during exercise 0.96 ± 0.46 and 0.91 ± 0.33 l min-1 mmHg-1, p=0.783). Peripheral hypercapnic chemosensitivity during mild exercise does not appear to be related to the development of EFL during exercise.

Supramaximal Testing to Confirm the Achievement of V̇O 2max in Acute Hypoxia.

PURPOSE: We sought to determine if supramaximal exercise testing confirms the achievement of V̇O 2max in acute hypoxia. We hypothesized that the incremental and supramaximal V̇O 2 will be sufficiently similar in acute hypoxia. METHODS: Twenty-one healthy adults (males n = 13, females n = 8) completed incremental and supramaximal exercise tests in normoxia and acute hypoxia (fraction inspired oxygen = 0.14) separated by at least 48 h. Incremental exercise started at 80 and 60 W in normoxia and 40 and 20 W in hypoxia for males and females, respectively, with all increasing by 20 W each minute until volitional exhaustion. After a 20-min postexercise rest period, a supramaximal test at 110% peak power until volitional exhaustion was completed. RESULTS: Supramaximal exercise testing yielded a lower V̇O 2 than incremental testing in hypoxia (3.11 ± 0.78 vs 3.21 ± 0.83 L·min -1 , P = 0.001) and normoxia (3.71 ± 0.91 vs 3.80 ± 1.02 L·min -1 , P = 0.01). Incremental and supramaximal V̇O 2 were statistically similar, using investigator-determined equivalence bounds ±150 mL·min -1 , in hypoxia ( P = 0.02, 90% confidence interval [CI] = 0.05-0.14) and normoxia ( P = 0.03, 90% CI = 0.01-0.14). Likewise, using ±2.1 mL·kg -1 ·min -1 bounds, incremental and supramaximal V̇O 2 values were statistically similar in hypoxia ( P = 0.04, 90% CI = 0.70-2.0) and normoxia ( P = 0.04, 90% CI = 0.30-2.0). CONCLUSIONS: Despite differences in the oxygen cascade, incremental and supramaximal V̇O 2 values were statistically similar in both hypoxia and normoxia, demonstrating the utility of supramaximal verification of V̇O 2max in the setting of acute hypoxia.

Peripheral hypercapnic chemosensitivity at rest and progressive exercise intensities in males and females.

Peripheral hypercapnic chemosensitivity (PHC) is the ventilatory response to hypercapnia and is enhanced with acute whole body exercise. However, little is known about the mechanism(s) responsible for the exercise-related increase in PHC and if progressive exercise leads to further augmentation. We hypothesized that unloaded cycle exercise (0 W) would increase PHC but progressively increasing the intensity would not further augment the response. Twenty healthy subjects completed two testing days. Day 1 was a maximal exercise test on a cycle ergometer to determine peak power output (Wmax). Day 2 consisted of six 12-min stages: 1) rest on chair, 2) rest on bike, 3) 0 W unloaded cycling, 4) 25% Wmax, 5) 50% Wmax, and 6) ∼70% Wmax with ∼10 min of rest between each exercise stage. In each stage, PHC was assessed via two breaths of 10% CO2 (∼21% O2) repeated five times with ∼45 s between each to ensure end-tidal CO2 ([Formula: see text]) and ventilation returned to baseline. Prestimulus [Formula: see text] was not different between rest and unloaded cycling (P = 0.478). There was a significant increase in PHC between seated rest and 25% Wmax (0.71 ± 0.37 vs. 1.03 ± 0.52 L·mmHg-1·min-1, respectively, P = 0.0006) and between seated rest and unloaded cycling (0.71 ± 0.37 vs. 1.04 ± 0.4 L·mmHg-1·min-1, respectively, P = 0.0017). There was no effect of exercise intensity on PHC (1.03 ± 0.52 vs. 0.95 ± 0.58 vs. 1.01 ± 0.65 L·mmHg-1·min-1 for 25, 50, and 70% Wmax, P = 0.44). The increased PHC response from seated rest to unloaded and 25% Wmax, but no effect of exercise intensity suggests a possible feedforward/feedback mechanism causing increased PHC sensitivity through the act of cycling.NEW & NOTEWORTHY Unloaded exercise significantly increased the peripheral hypercapnic ventilatory response (HCVR) compared with rest. However, increases in exercise intensity did not further augment peripheral HCVR. Males had a greater peripheral HCVR compared with females, but there was no interaction between sex and intensity. The lack of sex interactions suggests the mechanism augmenting the peripheral HCVR with exercise is independent of sex. The increase in peripheral HCVR with exercise is likely due to central command.

Perception of exercise-induced dyspnea after experimentally induced breathing discomfort.

The perception of dyspnea is influenced by both physiological and psychological factors. We sought to determine whether exertional dyspnea perception could be experimentally manipulated through prior exposure to heightened dyspnea while exercising. We hypothesized that dyspnea perception during exercise would be lower following an induced dyspnea task (IDT). Sixteen healthy participants (eight females, eight males) completed two days of exercise testing. Day 1 involved an incremental cycle exercise test starting at 40 W for females and 60 W for males, increasing by 20 W each minute until volitional exhaustion. Following the maximal exercise test on Day 1, participants completed IDT, involving 5 min of exercise at 70% of peak work rate with 500 mL dead space and external resistance (i.e., 6.8 ± 2.3 cm·H2O·s-1·L-1 inspiration, 3.8 ± 0.7 cm·H2O·s-1·L-1 expiration). Day 2 consisted of an incremental exercise test identical to Day 1. At maximal exercise, there were no differences in oxygen uptake (V̇O2; 44.7 ± 7.7 vs. 46.5 ± 6.3 mL·kg-1·min-1), minute ventilation (120 ± 35 vs. 127 ± 38 L·min-1), dyspnea (6.5 [4, 8.5] vs. 6 [4.25, 8.75]), or leg discomfort (6 [5, 8.75] vs. 7 [5, 9]) between days (all p > 0.05). At 60%-80% of peak V̇O2 (V̇O2peak), dyspnea was significantly lower on Day 2 (-0.75 [-1.375, 0] for 60% and -0.5 [0, -2] for 80%, p < 0.05) despite no differences in relevant physiological variables. The onset of perceived dyspnea occurred at a significantly higher exercise intensity on Day 2 than on Day 1 (42% ± 19% vs. 51% ± 17% V̇O2peak, respectively; p < 0.05). Except for 40% V̇O2peak (p = 0.05), RPE-L was not different at any intensities nor was the onset of perceived leg discomfort different between days (38% ± 14% vs. 43% ± 10% V̇O2peak, respectively; p = 0.10). Exposure to heightened dyspnea alters exercise-induced dyspnea perception during subsequent submaximal exercise bouts.

The Impact of Acetazolamide and Methazolamide on Exercise Performance in Normoxia and Hypoxia.

Doherty, Connor J., Jou-Chung Chang, Benjamin P. Thompson, Erik R. Swenson, Glen E. Foster, and Paolo B. Dominelli. The impact of acetazolamide and methazolamide on exercise performance in normoxia and hypoxia. High Alt Med Biol. 24:7-18, 2023.-Carbonic anhydrase (CA) inhibitors are commonly prescribed for acute mountain sickness (AMS). In this review, we sought to examine how two CA inhibitors, acetazolamide (AZ) and methazolamide (MZ), affect exercise performance in normoxia and hypoxia. First, we briefly describe the role of CA inhibition in facilitating the increase in ventilation and arterial oxygenation in preventing and treating AMS. Next, we detail how AZ affects exercise performance in normoxia and hypoxia and this is followed by a discussion on MZ. We emphasize that the overarching focus of the review is how the two drugs potentially affect exercise performance, rather than their ability to prevent/treat AMS per se, their interrelationship will be discussed. Overall, we suggest that AZ hinders exercise performance in normoxia, but may be beneficial in hypoxia. Based upon head-to-head studies of AZ and MZ in humans on diaphragmatic and locomotor strength in normoxia, MZ may be a better CA inhibitor when exercise performance is crucial at high altitude.

The effect of inspiratory muscle training and detraining on the respiratory metaboreflex.

NEW FINDINGS: What is the central question of this study? Is the attenuation of the respiratory muscle metaboreflex preserved after detraining? What is the main finding and its importance? Inspiratory muscle training increased respiratory muscle strength and attenuated the respiratory muscle metaboreflex as evident by lower heart rate and blood pressure. After 5 weeks of no inspiratory muscle training (detraining), respiratory muscle strength was still elevated and the metaboreflex was still attenuated. The benefits of inspiratory muscle training persist after cessation of training, and attenuation of the respiratory metaboreflex follows changes in respiratory muscle strength. ABSTRACT: Respiratory muscle training (RMT) improves respiratory muscle (RM) strength and attenuates the RM metaboreflex. However, the time course of muscle function loss after the absence of training or 'detraining' is less known and some evidence suggest the respiratory muscles atrophy faster than other muscles. We sought to determine the RM metaboreflex in response to 5 weeks of RMT and 5 weeks of detraining. An experimental group (2F, 6M; 26 ± 4years) completed 5 weeks of RMT and tibialis anterior (TA) training (each 5 days/week at 50% of maximal inspiratory pressure (MIP) and 50% maximal isometric force, respectively) followed by 5 weeks of no training (detraining) while a control group (1F, 7M; 24 ± 1years) underwent no intervention. Prior to training (PRE), post-training (POST) and post-detraining (DETR), all participants underwent a loaded breathing task (LBT) to failure (60% MIP) while heart rate and mean arterial blood pressure (MAP) were measured. Five weeks of training increased RM (18 ± 9%, P < 0.001) and TA (+34 ± 19%, P < 0.001) strength and both remained elevated after 5 weeks of detraining (MIP-POST vs. MIP-DETR: 154 ± 31 vs. 153 ± 28 cmH2O, respectively, P = 0.853; TA-POST vs. TA-DETR: 86 ± 19 vs. 85 ± 16 N, respectively, P = 0.982). However, the rise in MAP during LBT was attenuated POST (-11 ± 17%, P = 0.003) and DETR (-9 ± 9%, P = 0.007) during the iso-time LBT. The control group had no change in MIP (P = 0.33), TA strength (P = 0.385), or iso-time MAP (P = 0.867) during LBT across all time points. In conclusion, RM and TA have similar temporal strength gains and the attenuation of the respiratory muscle metaboreflex remains after 5 weeks of detraining.

Altering magnetic field strength impacts the assessment of diaphragmatic function using cervical magnetic stimulation.

Quantifying diaphragm neuromuscular function using cervical magnetic stimulation (CMS) typically uses only a single stimulator (1-Stim) which may be inadequate to maximally stimulate the phrenic nerves. We questioned if using two stimulators (2-Stim) together alters diaphragm neuromuscular function at baseline and following inspiratory pressure threshold loading. Six (n = 3 female) healthy young participants were instrumented with esophageal and gastric balloon tipped catheters and electrodes over the 7-8th intercostal space. With either 1-Stim or 2-Stim an incremental protocol, where the stimulator intensity was progressively increased was completed prior to a series of potentiated twitches. The inspiratory threshold loading test consisted of loaded breathing to failure. Compared to 1-Stim, 2-Stim resulted in significantly greater unpotentiated Pditw and M-waves during the incremental protocol (both p < 0.01). Similarly, 2-Stim resulted in greater potentiated Pditw (31 ± 8 vs. 41 ± 9 cmH2O; p = 0.02) and M-waves (6.4 ± 2.9 vs. 8.6 ± 2.4 V; p = 0.02). Our findings suggest that CMS using 1-Stim is unlikely to generate a sufficient magnetic field to maximally stimulate the phrenic nerves and may underestimate diaphragm function.

Peripheral hypercapnic chemosensitivity in trained and untrained females and males during exercise.

Hypercapnic chemosensitivity is the response to the increased partial pressure of carbon dioxide and results from central and peripheral chemosensor stimulation. The hypercapnic chemosensitivity of the peripheral chemoreceptors is potentially impacted by acute exercise, aerobic fitness, and sex. We sought to determine the peripheral chemoresponse to transient hypercapnia at rest and during exercise in males and females of various fitness. We hypothesized that 1) higher fitness participants would have lower hypercapnic chemosensitivity compared with those with lower fitness and 2) males would have a higher chemoresponse than females. Forty healthy participants (20 females) participated in one test day involving transient hypercapnic chemosensitivity testing and a maximal exercise test. Chemosensitivity testing involved two breaths of 10% CO2 repeated five times (45 s to 1 min between repeats) at rest and the first two stages of a maximal exercise test. There was no significant difference between higher and lower aerobic fitness groups, (mean difference 0.23 ± 0.22 rest; -0.07 ± 0.04 stage 1; 0.11 ± 0.17 stage 2 L/mmHg·min) during each stage (P = 0.472). However, we saw a significant increase in the hypercapnic response during stage 1 (0.98 ± 0.4 L/mmHg·min) compared with rest (0.79 ± 0.5 L/mmHg·min; P = 0.01). Finally, at 80 W, males had a higher chemoresponse compared with females, which persisted following body surface area correction (0.56 ± 0.2 vs. 0.42 ± 0.2 L/mmHg·min·m2, for females and males respectively (P = 0.038). Our findings suggest that sex, unlike aerobic fitness, influences peripheral hypercapnic chemosensitivity and that context (i.e., rest vs. exercise) is an important consideration.NEW & NOTEWORTHY The hypercapnic chemoresponse to transient CO2 showed an increase during acute physical activity; however, this response did not persist with further increases in intensity and was not different between participants of different aerobic fitness. Males and females show a differing response to CO2 during exercise when compared with an iso-V̇co2. Our results suggest that adaptations that lead to increased aerobic fitness do not impact the hypercapnic ventilatory response but there is an effect of sex.

Evaluation of sex-based differences in airway size and the physiological implications.

Recent evidence suggests healthy females have significantly smaller central conducting airways than males when matched for either height or lung volume during analysis. This anatomical sex-based difference could impact the integrative response to exercise. Our review critically evaluates the literature on direct and indirect techniques to measure central conducting airway size and their limitations. We present multiple sources highlighting the difference between male and female central conducting airway size in both pediatric and adult populations. Following the discussion of measurement techniques and results, we discuss the functional implications of these differences in central conducting airway size, including work of breathing, oxygen cost of breathing, and how these impacts will continue into elderly populations. We then discuss a range of topics for the future direction of airway differences and the benefits they could provide to both healthy and diseased populations. Specially, these sex-differences in central conducting airway size could result in different aerosol deposition or how lung disease manifests. Finally, we detail emerging techniques that uniquely allow for high-resolution imaging to be paired with detailed physiological measures.

Impact of wearing a surgical and cloth mask during cycle exercise.

We sought to determine the impact of wearing cloth or surgical masks on the cardiopulmonary responses to moderate-intensity exercise. Twelve subjects (n = 5 females) completed three, 8-min cycling trials while breathing through a non-rebreathing valve (laboratory control), cloth, or surgical mask. Heart rate (HR), oxyhemoglobin saturation (SpO2), breathing frequency, mouth pressure, partial pressure of end-tidal carbon dioxide (PetCO2) and oxygen (PetO2), dyspnea were measured throughout exercise. A subset of n = 6 subjects completed an additional exercise bout without a mask (ecological control). There were no differences in breathing frequency, HR or SpO2 across conditions (all p > 0.05). Compared with the laboratory control (4.7 ± 0.9 cmH2O [mean ± SD]), mouth pressure swings were smaller with the surgical mask (0.9 ± 0.7; p < 0.0001), but similar with the cloth mask (3.6 ± 4.8 cmH2O; p = 0.66). Wearing a cloth mask decreased PetO2 (-3.5 ± 3.7 mm Hg) and increased PetCO2 (+2.0 ± 1.3 mm Hg) relative to the ecological control (both p < 0.05). There were no differences in end-tidal gases between mask conditions and laboratory control (both p > 0.05). Dyspnea was similar between the control conditions and the surgical mask (p > 0.05) but was greater with the cloth mask compared with laboratory (+0.9 ± 1.2) and ecological (+1.5 ± 1.3) control conditions (both p < 0.05). Wearing a mask during short-term moderate-intensity exercise may increase dyspnea but has minimal impact on the cardiopulmonary response. Novelty: Wearing surgical or cloth masks during exercise has no impact on breathing frequency, tidal volume, oxygenation, and heart rate However, there are some changes in inspired and expired gas fractions that are physiologically irrelevant. In young healthy individuals, wearing surgical or cloth masks during submaximal exercise has few physiological consequences.

Arterial baroreflex regulation of muscle sympathetic nerve activity at rest and during stress.

KEY POINTS: The arterial baroreflex controls vasoconstrictor muscle sympathetic nerve activity (MSNA) in a negative feedback manner by increasing or decreasing activity during spontaneous blood pressure falls or elevations, respectively. Spontaneous sympathetic baroreflex sensitivity is commonly quantified as the slope of the relationship between MSNA burst incidence or strength and beat-to-beat variations in absolute diastolic blood pressure. We assessed the relationships between blood pressure inputs related to beat-to-beat blood pressure change or blood pressure rate-of-change (variables largely independent of absolute pressure) and MSNA at rest and during exercise and mental stress. The number of participants with strong linear relationships between MSNA and beat-to-beat diastolic blood pressure change variables or absolute diastolic blood pressure were similar at rest, although during stress the beat-to-beat diastolic blood pressure change variables were superior. Current methods may not fully characterize the capacity of the arterial baroreflex to regulate MSNA. ABSTRACT: Spontaneous sympathetic baroreflex sensitivity (sBRS) is commonly quantified as the slope of the relationship between variations in absolute diastolic blood pressure (DBP) and muscle sympathetic nerve activity (MSNA) burst incidence or strength. This relationship is well maintained at rest but not during stress. We assessed whether sBRS could be calculated at rest and during stress (static handgrip, rhythmic handgrip, mental stress) using blood pressure variables that quantify relative change: beat-to-beat DBP change (ΔDBP), ΔDBP rate-of-change (ΔDBP rate), pulse pressure (PP) and PP rate-of-change (PP rate). Sixty-six healthy participants underwent continuous measures of blood pressure (finger photoplethysmography) and multi-unit MSNA (microneurography). At rest, absolute DBP (91%), ΔDBP (97%) and ΔDBP rate (97%) each yielded higher proportions of participants with strong linear relationships (r ≥ 0.6) with MSNA burst incidence compared to PP (57%) and PP rate (56%) and produced similar sBRS slopes (DBP: -4.5 ± 2.0 bursts 100 heartbeats-1 /mmHg; ΔDBP: -5.0 ± 2.1 bursts 100 heartbeats-1 /ΔmmHg; ΔDBP rate: -4.9 ± 2.2 bursts 100 heartbeats-1 /ΔmmHg s-1 ; P > 0.05). During stress, ΔDBP (74%) and ΔDBP rate (74%) yielded higher proportions of strong linear relationships with MSNA burst incidence than absolute DBP (43%), PP (46%) and PP rate (49%) (all P < 0.05). The absolute DBP associated with a 50% chance of a MSNA burst (T50 ) was shifted rightward during static handgrip (Δ+15 ± 11 mmHg, P < 0.001) and mental stress (Δ+11 ± 7 mmHg, P < 0.001); however, the ΔDBP T50 was shifted rightward during static handgrip (Δ+2.5 ± 3.7 mmHg, P = 0.009) but not mental stress (Δ0.0 ± 4.4 mmHg, P = 0.99). These findings suggest that calculating sBRS using absolute DBP alone may not adequately characterize arterial baroreflex regulation of MSNA, particularly during stress.

Effects of dynamic arm and leg exercise on muscle sympathetic nerve activity and vascular conductance in the inactive leg.

The influence of muscle sympathetic nerve activity (MSNA) responses on local vascular conductance during exercise are not well established. Variations in exercise mode and active muscle mass can produce divergent MSNA responses. Therefore, we sought to examine the effects of small- versus large-muscle mass dynamic exercise on vascular conductance and MSNA responses in the inactive limb. Thirty-five participants completed two study visits in a randomized order. During visit 1, superficial femoral artery (SFA) blood flow (Doppler ultrasound) was assessed at rest and during steady-state rhythmic handgrip (RHG; 1:1 duty cycle, 40% maximal voluntary contraction), one-leg cycling (17 ± 3% peak power output), and concurrent exercise at the same intensities. During visit 2, MSNA (contralateral fibular nerve microneurography) was acquired successfully in 12/35 participants during the same exercise modes. SFA blood flow increased during RHG (P < 0.0001) and concurrent exercise (P = 0.03) but not cycling (P = 0.91). SFA vascular conductance was unchanged during RHG (P = 0.88) but reduced similarly during concurrent and cycling exercise (both P < 0.003). RHG increased MSNA burst frequency (P = 0.04) without altering burst amplitude (P = 0.69) or total MSNA (P = 0.26). In contrast, cycling and concurrent exercise had no effects on MSNA burst frequency (both P ≥ 0.10) but increased burst amplitude (both P ≤ 0.001) and total MSNA (both P ≤ 0.007). Across all exercise modes, the changes in MSNA burst amplitude and SFA vascular conductance were correlated negatively (r = -0.43, P = 0.02). In summary, the functional vascular consequences of alterations in sympathetic outflow to skeletal muscle are most closely associated with changes in MSNA burst amplitude, but not frequency, during low-intensity dynamic exercise.NEW & NOTEWORTHY Low-intensity small- versus large-muscle mass exercise can elicit divergent effects on muscle sympathetic nerve activity (MSNA). We examined the relationships between changes in MSNA (burst frequency and amplitude) and superficial femoral artery (SFA) vascular conductance during rhythmic handgrip, one-leg cycling, and concurrent exercise in the inactive leg. Only changes in MSNA burst amplitude were inversely associated with SFA vascular conductance responses. This result highlights the functional importance of measuring MSNA burst amplitude during exercise.

Microneurographic characterization of sympathetic responses during 1-leg exercise in young and middle-aged humans.

Muscle sympathetic nerve activity (MSNA) at rest increases with age. However, the influence of age on MSNA recorded during dynamic leg exercise is unknown. We tested the hypothesis that aging attenuates the sympatho-inhibitory response observed in young subjects performing mild to moderate 1-leg cycling. After predetermining peak oxygen uptake, we compared contra-lateral fibular nerve MSNA during 2 min each of mild (unloaded) and moderate (30%-40% of the work rate at peak oxygen uptake, halved for single leg) 1-leg cycling in 18 young (age, 23 ± 1 years (mean ± SE)) and 18 middle-aged (age, 57 ± 2 years) sex-matched healthy subjects. Mean height, weight, resting heart rate, systolic blood pressure, and percent predicted peak oxygen uptake were similar between groups. Middle-aged subjects had higher resting MSNA burst frequency and incidence (P < 0.001) and diastolic blood pressure (P = 0.04). During moderate 1-leg cycling, older subjects' systolic blood pressure increased more (+21 ± 5 vs. +10 ± 1 mm Hg; P = 0.02) and their fall in MSNA burst incidence was amplified (-19 ± 2 vs. -11 ± 2 bursts/100 heart beats; P = 0.01) but because heart rate rose less (+15 ± 3 vs. +19 ± 2 bpm; P = 0.03), exercise induced similar reductions in burst frequency (P = 0.25). Contrary to our initial hypothesis, with advancing age, mild- to moderate-intensity dynamic leg exercise elicits a greater rise in systolic blood pressure and a larger fall in MSNA.

Evidence for differential control of muscle sympathetic single units during mild sympathoexcitation in young, healthy humans.

Two subpopulations of muscle sympathetic single units with opposite discharge characteristics have been identified during low-level cardiopulmonary baroreflex loading and unloading in middle-aged adults and patients with heart failure. The present study sought to determine whether similar subpopulations are present in young healthy adults during cardiopulmonary baroreflex unloading ( study 1) and rhythmic handgrip exercise ( study 2). Continuous hemodynamic and multiunit and single unit muscle sympathetic nerve activity (MSNA) data were collected at baseline and during nonhypotensive lower body negative pressure (LBNP; n = 12) and 40% maximal voluntary contraction rhythmic handgrip exercise (RHG; n = 24). Single unit MSNA responses were classified as anticipated or paradoxical based on whether changes were concordant or discordant with the multiunit MSNA response, respectively. LBNP and RHG both increased multiunit MSNA burst frequency (∆5 ± 3 bursts/min, P < 0.001; ∆5 ± 8 bursts/min, P = 0.005), burst amplitude (∆5 ± 7%, P = 0.04; ∆13 ± 14%, P < 0.001), and total MSNA (∆302 ± 191 AU/min, P = 0.001; ∆585 ± 556 AU/min, P < 0.001). During LBNP and RHG, 43 and 64 muscle single units were identified, respectively, which increased spike frequency (∆9 ± 11 spikes/min, P < 0.001; ∆10 ± 19 spikes/min, P < 0.001) and the probability of multiple spike firing (∆10 ± 12%, P < 0.001; ∆11 ± 26%, P = 0.001). During LBNP and RHG, 36 (84%) and 39 (61%) single units possessed anticipated firing responses (∆12 ± 10 spikes/min, P < 0.001; ∆19 ± 19 spikes/min, P < 0.001), whereas 7 (16%) and 25 (39%) single units exhibited paradoxical reductions (∆-3 ± 1 spikes/min, P = 0.003; ∆-4 ± 5 spikes/min, P < 0.001). The observation of divergent subpopulations of muscle sympathetic single units in healthy young humans during two mild sympathoexcitatory stressors supports differential control at the fiber level as a fundamental characteristic of human sympathetic regulation. NEW & NOTEWORTHY The activity of muscle sympathetic single units was recorded during cardiopulmonary baroreceptor unloading and rhythmic handgrip exercise in young healthy humans. During both stressors, the majority of single units (84% and 61%) exhibited anticipated behavior concordant with the integrated muscle sympathetic response, whereas a smaller proportion (16% and 39%) exhibited paradoxical sympathoinhibition. These results support differential control of postganglionic muscle sympathetic fibers as a characteristic of human sympathetic regulation during mild sympathoexcitatory stress. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/differential-control-of-sympathetic-outflow-in-young-humans/ .

TRPV1 and BDKRB2 receptor polymorphisms can influence the exercise pressor reflex.

KEY POINTS: The mechanisms responsible for the high inter-individual variability in blood pressure responses to exercise remain unclear. Common genetic variants of genes related to the vascular transduction of sympathetic outflow have been investigated, but variants influencing skeletal muscle afferent feedback during exercise have not been explored. Single nucleotide polymorphisms in TRPV1 rs222747 and BDKRB2 rs1799722 receptors present in skeletal muscle were associated with differences in the magnitude of the blood pressure response to static handgrip exercise but not mental stress. The combined effects of TRPV1 rs222747 and BDKRB2 rs1799722 on blood pressure and heart rate responses during exercise were additive, and primarily found in men. Genetic differences in skeletal muscle metaboreceptors may be a risk factor for exaggerated blood pressure responses to exercise. ABSTRACT: Exercise blood pressure (BP) responses demonstrate high inter-individual variability, which could relate to differences in metabolically sensitive afferent feedback from the exercising muscle. We hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding metaboreceptors present in group III/IV skeletal muscle afferents can influence the exercise pressor response. Two hundred men and women underwent measurements of continuous BP and heart rate at baseline and during 2 min of static handgrip exercise (30% maximal volitional contraction), post-exercise circulatory occlusion and mental stress (serial subtraction; internal control). Participants were genotyped for SNPs in TRPV1 (rs222747; G/C), ASIC3 (rs2288645; G/A), BDKRB2 (rs1799722; C/T), PTGER2 (rs17197; A/G) and P2RX4 (rs25644; A/G). Exercise systolic BP (19 ± 10 vs. 22 ± 10 mmHg, P = 0.03) was lower in GG versus GC/CC minor allele carriers for TRPV1 rs222747, while exercise diastolic BP (14 ± 7 vs. 17 ± 7 mmHg, P = 0.007) and heart rate (12 ± 8 vs. 15 ± 9 beats min-1 , P = 0.03) were lower in CC versus CT/TT minor allele carriers for BDKRB2 rs1799722. Individuals carrying both minor alleles for TRPV1 rs222747 and BDKRB2 rs1799722 had greater systolic (22 ± 11 vs. 17 ± 10 mmHg, P = 0.04) and diastolic (18 ± 7 vs. 14 ± 7 mmHg, P = 0.01) BP responses than those with no minor alleles; these differences were larger in men. No differences in BP or heart rate responses were detected during static handgrip with ASIC3 rs2288645, PTGER2 rs17197 or P2RX4 rs25644. None of the selected SNPs were associated with differences during mental stress. These findings demonstrate that variants in TRPV1 and BDKRB2 receptors can contribute to BP differences during static exercise in an additive manner.

Comparison of laboratory and ambulatory measures of central blood pressure and pulse wave reflection: hitting the target or missing the mark?

Prior studies demonstrating clinical significance of noninvasive estimates of central blood pressure (BP) and pulse wave reflection have relied primarily on discrete resting measures. The aim of this study was to compare central BP and pulse wave reflection measures sampled during a single resting laboratory visit against those obtained under ambulatory conditions. The secondary aim was to investigate the reproducibility of ambulatory central BP and pulse wave reflection measurements. Forty healthy participants (21 males; 24 ± 3 years) completed three measurements of brachial artery pulse wave analysis (Oscar 2 with SphygmoCor Inside) in the laboratory followed by 24 hours of ambulatory monitoring. Seventeen participants repeated the 24-hour ambulatory monitoring visit after at least 1 week. Ambulatory measures were divided into daytime (9 AM-9 PM), nighttime (1 AM-6 AM), and 24-hour periods. Compared with laboratory measurements, central systolic BP, augmentation pressure, and augmentation index (with and without heart rate normalization) were higher (all P < .01) during daytime and 24-hour periods but lower during the nighttime period (all P < .001). The drop in nighttime brachial systolic BP was larger than central systolic pressure (Δ -20 ± 6 vs. -15 ± 6 mm Hg; P < .0001). Repeat ambulatory measurements of central BP and pulse wave reflection displayed good-to-excellent intraclass correlation coefficients (r = 0.58-0.86; all P < .01), although measures of pulse wave reflection had higher coefficients of variation (14%-41%). The results highlight absolute differences in central BP and pulse wave reflection between discrete laboratory and ambulatory conditions. The use of ambulatory measures of central BP and pulse wave reflection warrant further investigation for clinical prognostic value.

Interindividual variability in muscle sympathetic responses to static handgrip in young men: evidence for sympathetic responder types?

Negative and positive muscle sympathetic nerve activity (MSNA) responders have been observed during mental stress. We hypothesized that similar MSNA response patterns could be identified during the first minute of static handgrip and contribute to the interindividual variability throughout exercise. Supine measurements of multiunit MSNA (microneurography) and continuous blood pressure (Finometer) were recorded in 29 young healthy men during the first (HG1) and second (HG2) minute of static handgrip (30% maximal voluntary contraction) and subsequent postexercise circulatory occlusion (PECO). Responders were identified on the basis of differences from the typical error of baseline total MSNA: 7 negative, 12 positive, and 10 nonresponse patterns. Positive responders demonstrated larger total MSNA responses during HG1 ( P < 0.01) and HG2 ( P < 0.0001); however, the increases in blood pressure throughout handgrip exercise were similar between all groups, as were the changes in heart rate, stroke volume, cardiac output, total vascular conductance, and respiration (all P > 0.05). Comparing negative and positive responders, total MSNA responses were similar during PECO ( P = 0.17) but opposite from HG2 to PECO (∆40 ± 46 vs. ∆-21 ± 62%, P = 0.04). Negative responders also had a shorter time-to-peak diastolic blood pressure during HG1 (20 ± 20 vs. 44 ± 14 s, P < 0.001). Total MSNA responses during HG1 were associated with responses to PECO ( r = 0.39, P < 0.05), the change from HG2 to PECO ( r = -0.49, P < 0.01), and diastolic blood pressure time to peak ( r = 0.50, P < 0.01). Overall, MSNA response patterns during the first minute of static handgrip contribute to interindividual variability and appear to be influenced by differences in central command, muscle metaboreflex activation, and rate of loading of the arterial baroreflex.

Muscle sympathetic nerve responses to passive and active one-legged cycling: insights into the contributions of central command.

The contribution of central command to the peripheral vasoconstrictor response during exercise has been investigated using primarily handgrip exercise. The purpose of the present study was to compare muscle sympathetic nerve activity (MSNA) responses during passive (involuntary) and active (voluntary) zero-load cycling to gain insights into the effects of central command on sympathetic outflow during dynamic exercise. Hemodynamic measurements and contralateral leg MSNA (microneurography) data were collected in 18 young healthy participants at rest and during 2 min of passive and active zero-load one-legged cycling. Arterial baroreflex control of MSNA burst occurrence and burst area were calculated separately in the time domain. Blood pressure and stroke volume increased during exercise ( P < 0.0001) but were not different between passive and active cycling ( P > 0.05). In contrast, heart rate, cardiac output, and total vascular conductance were greater during the first and second minute of active cycling ( P < 0.001). MSNA burst frequency and incidence decreased during passive and active cycling ( P < 0.0001), but no differences were detected between exercise modes ( P > 0.05). Reductions in total MSNA were attenuated during the first ( P < 0.0001) and second ( P = 0.0004) minute of active compared with passive cycling, in concert with increased MSNA burst amplitude ( P = 0.02 and P = 0.005, respectively). The sensitivity of arterial baroreflex control of MSNA burst occurrence was lower during active than passive cycling ( P = 0.01), while control of MSNA burst strength was unchanged ( P > 0.05). These results suggest that central feedforward mechanisms are involved primarily in modulating the strength, but not the occurrence, of a sympathetic burst during low-intensity dynamic leg exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity burst frequency decreased equally during passive and active cycling, but reductions in total muscle sympathetic nerve activity were attenuated during active cycling. These results suggest that central command primarily regulates the strength, not the occurrence, of a muscle sympathetic burst during low-intensity dynamic leg exercise.

Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity.

PURPOSE: Overload training is hypothesized to alter autonomic regulation, although interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. METHODS: Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in 17 healthy triathletes and cyclists after 1 wk of reduced training (baseline) and again after 3 wk of either regular (n = 7) or overload (n = 10) training. RESULTS: After training, the changes (Δ) in peak power output (10 ± 10 vs -12 ± 9 W, P < 0.001), maximal heart rate (-2 ± 4 vs -8 ± 3 bpm, P = 0.006), heart rate variability (SD of normal-to-normal intervals, 27 ± 31 vs -3 ± 25 ms; P = 0.04), and cardiac BRS (7 ± 6 vs -2 ± 8 ms·mm Hg, P = 0.02) differed between the control and overload groups. The change in MSNA burst frequency (-2 ± 2 vs 4 ± 5 bursts per minute, P = 0.02) differed between groups. Across all participants, the changes in resting MSNA and peak power output were correlated negatively (r = -0.51, P = 0.04). No between-group differences in resting heart rate or blood pressure were observed (all P > 0.05). CONCLUSIONS: Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations after overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance.