American journal of physiology. Regulatory, integrative and comparative physiology最新文献

The cerebral vasodilator response to increased arterial carbon dioxide (CO₂) concentration, termed cerebral vasomotor reactivity (CVMR), is used to assess cerebral vascular function. We sought to assess the within-day and between-day repeatability of CVMR to rebreathing-induced hypercapnia. Twelve healthy adults performed a within-day short interval protocol (17 ± 2 min between trials), ten performed a within-day long interval protocol (145 ± 16 min between trials), and seventeen performed a between-day protocol (5 ± 2 days between visits). Repeatability of the slope of the percent change in middle cerebral artery mean blood velocity (%MCAv_mean) and cerebral vascular conductance index (%CVCi), to the change in partial pressure of end-tidal CO₂ ([Formula: see text]) between the two trials/days was assessed. Within-day short interval, %MCAv_mean slope demonstrated fair to excellent repeatability (intraclass correlation, ICC = 0.92 [95% confidence interval 0.72-0.98]; P < 0.001) while %CVCi slope showed more variability (ICC = 0.84 [0.47-0.95]; P = 0.002]). Within-day long interval, %MCAv_mean (ICC = 0.95 [0.80-0.99]) and %CVCi (ICC = 0.94 [0.71-0.99]) slopes showed good to excellent and fair to excellent repeatability respectively (P < 0.001 for both). For between-day trials, better repeatability was observed for %CVCi (ICC = 0.85 [0.57-0.95]; P < 0.001) compared with %MCAv_mean (ICC = 0.76 [0.33-0.91]; P = 0.004) slope. These findings indicate repeatable within- and between-day CVMR responses to rebreathe-induced hypercapnia. However, a longer interval may be better for within-day repeat trials, particularly for CVCi measures.NEW & NOTEWORTHY The cerebral vasodilator response to increases in arterial carbon dioxide concentration, termed cerebral vasomotor reactivity, provides an index of cerebral vascular function/health. Reduced responses are present in populations with elevated cerebral vascular and neurocognitive disease risk/overt disease. Cerebral vasomotor reactivity is often assessed during rebreathing-induced hypercapnia. This study determined that the day-to-day and between-day variability in this response is repeatable, thereby providing important methodological information to the scientific community.

Although existing literature covers significant detail on the physiology of human freediving, the lack of standardized protocols has hindered comparisons due to confounding variables such as exercise and depth. By accounting for these variables, direct depth-dependent impacts on cardiovascular and blood oxygen regulation can be investigated. In this study, depth-dependent effects on 1) cerebral hemodynamic and oxygenation changes, 2) arterial oxygen saturation ([Formula: see text]), and 3) heart rate during breath-hold diving without confounding effects of exercise were investigated. Six freedivers (51.0 ± 12.6 yr; means ± SD), instrumented with continuous-wave near-infrared spectroscopy for monitoring cerebral hemodynamic and oxygenation measurements, heart rate, and [Formula: see text], performed sled-assisted breath-hold dives to 15 m and 42 m. Arterial blood gas tensions were validated through cross-sectional periodic blood sampling. Cerebral hemodynamic changes were characteristic of breath-hold diving, with changes during ascent from both depths likely driven by decreasing [Formula: see text] due to lung expansion. Although [Formula: see text] was significantly lower following 42-m dives [t(5) = -4.183, P < 0.05], mean cerebral arterial-venous blood oxygen saturation remained at 74% following dives to both depths. Cerebral oxygenation during ascent from 42 m may have been maintained through increased arterial delivery. Heart rate was variable with no significant difference in minimum heart rate between both depths [t(5) = -1.017, P > 0.05]. This study presents a standardized methodology, which could provide a basis for future research on human freediving physiology and uncover ways in which freedivers can reduce potential risks of the sport.NEW & NOTEWORTHY We present a standardized methodology in which trained breath-hold divers instrumented with wearable near-infrared spectroscopy (NIRS) technology and a cannula for arterial blood sampling completed sled-assisted dives to two different dive depths to account for the confounding factors of exercise and depth during breath-hold diving. In our investigation, we highlight the utility of wearable NIRS systems for continuous hemodynamic and oxygenation monitoring to investigate the impacts of hydrostatic pressure on cardiovascular and blood oxygen regulation.

Ribosome biogenesis is an important regulator of skeletal muscle hypertrophy induced by repeated bouts of resistance exercise (RE). Hot-water immersion (HWI), a widely used post-exercise recovery strategy, activates the mechanistic target of rapamycin (mTOR) signaling, a key regulator of ribosome biogenesis in skeletal muscle. However, the effect of HWI on skeletal muscle ribosome biogenesis is not well understood. Here, we aimed to investigate the effects of HWI and post-exercise HWI on ribosome biogenesis using a rat RE model. Male Sprague-Dawley rats were randomly assigned to HWI and non-HWI groups. In both groups, the right leg was isometrically exercised using transcutaneous electrical stimulation, while the left leg was used as an internal non-RE control. Following RE, both limbs were immersed in hot water (41.2 ± 0.03°C) for 20 min under isoflurane anesthesia in the HWI group and the gastrocnemius muscles were sampled at 3- and 24-h post-exercise. HWI significantly increased mTOR signaling and c-Myc mRNA expression, whereas post-exercise HWI significantly increased transcription initiation factor-IA mRNA expression. However, neither HWI nor post-exercise HWI enhanced 45S pre-rRNA expression, ribosomal RNA, or ribosomal protein content. In addition, HWI tended to decrease 28S rRNA and 18S rRNA content, widely used markers of ribosome content. These results suggest that HWI as a post-exercise recovery is not effective in activating ribosome biogenesis.NEW & NOTEWORTHY Ribosome biogenesis is crucial in resistance exercise (RE)-induced skeletal muscle hypertrophy. This study examined the effects of hot-water immersion (HWI) on ribosome biogenesis after RE. HWI and post-exercise HWI increased c-Myc and transcription initiation factor-IA mRNA but did not alter ribosomal RNA transcription or ribosomal protein content. HWI tended to decrease 28S and 18S ribosomal RNA. These findings suggest that HWI, as a recovery strategy, does not effectively promote ribosome biogenesis or muscle protein synthesis.

Despite some evidence, the role of sympathetic nerve activity in the regulation of cerebral blood flow remains controversial. In humans, muscle sympathetic nervous activity (MSNA) is the only direct measure of sympathetic nerve activity that can be recorded with sufficient temporal resolution to allow association with dynamic regulation of cerebral blood velocity (CBv). This study tested the hypothesis that MSNA is associated with the regulation of CBv at rest and during different physiological maneuvers. Nine healthy subjects underwent two sympathoexcitatory maneuvers: 1) isometric handgrip exercise (HGR), and 2) cold pressor test (CPT). Mean arterial pressure (MAP; oscillometric method), CBv (transcranial Doppler ultrasound), and MSNA (microneurography) were measured continuously during experimental protocols. Ordinary and partial coherences of the MAP, CBv, and MSNA time series were estimated by transfer function analysis in the low-frequency range (0.07-0.20 Hz), using MAP and MSNA as inputs and CBv as the output variable. When the influence of MSNA was taken into account, the partial coherences between MAP and CBv were considerably reduced at baseline (P < 0.01), HGR (P = 0.02), and CPT (P < 0.01). Similarly, when the influence of MAP was taken into account, the coherence between MSNA and CBv was considerably reduced at baseline (P < 0.01), HGR (P = 0.02), and CPT (P = 0.01), leading to the conclusion, that MSNA was associated to dynamic regulation of CBv. Partial coherence analysis is a promising method for assessing the influence of the sympathetic nervous system on cerebral hemodynamics.NEW & NOTEWORTHY Partial coherence analysis has been instrumental in demonstrating, for the first time, that cerebral blood velocity (CBv) is continuously influenced, not only by fluctuations in mean arterial pressure but also muscle sympathetic nervous activity (MSNA), leading to similar dynamic responses at rest and during different sympathoexcitatory maneuvers in healthy subjects. Modeling the temporal relationship between MSNA and CBv opens new opportunities for advancing knowledge regarding the role of the sympathetic nervous system in the regulation of cerebral circulation in health and disease.

Antimicrobial peptides, key players of innate mucosal immunity in the oral cavity, exert antibacterial and bacteriolytic effects. This study aimed to clarify the effects of acute exercise at different intensities and durations on salivary antimicrobial peptide levels. In a randomized crossover trial, 14 young healthy untrained men performed intensity trials [cycling at 35%, 55%, and 75% of maximal oxygen uptake (V̇o_2max) for 30 min] and duration trials (cycling at 55% V̇o_2max for 30, 60, and 90 min). Saliva samples were collected at baseline and 0 and 60 min after exercise. In intensity trials, the change in salivary lactoferrin levels from baseline to 0 min after 30 min exercise was greater at 75% V̇o_2max exercise intensity compared with that at 35% V̇o_2max. Furthermore, the change in salivary human β-defensin-2 (HBD-2) levels was greater at 75% V̇o_2max compared with that at 35% and 55% V̇o_2max. Salivary lysozyme levels increased after exercise, independent of exercise intensity. However, salivary LL-37 levels did not change after exercise at any intensity. In addition, in duration trials, the change in salivary levels of LL-37 and HBD-2 from baseline to 0 min after exercise at 55% V̇o_2max was greater after 60 and 90 min of exercise compared with that after 30 min of exercise. However, salivary lactoferrin and lysozyme levels increased after exercise, independent of exercise duration. Our findings suggest that secretory responses to acute exercise with exercise intensity and duration differ among salivary antimicrobial peptides.NEW & NOTEWORTHY We investigated the effects of acute exercise at different intensities and durations on the immune response to salivary antimicrobial peptides in young healthy men. Levels of four salivary antimicrobial peptides increased after exercise dependently or independently of exercise intensity and duration, whereas some salivary antimicrobial peptides did not change after exercise. These findings suggest that the secretory responses to acute exercise with different intensities and durations differ among salivary antimicrobial peptides.

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVC_max) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVC_max in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.NEW & NOTEWORTHY We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.

Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: 1) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and 2) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (aim 1). After a recovery period, participants completed a cold pressor test (CPT; aim 2). Addressing the first aim, tolerance to LBNP was not different between trials (P = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time P < 0.001, trial P = 0.477, interaction P = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time P < 0.001, trial P = 0.626, interaction P = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (P < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (P = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.NEW & NOTEWORTHY Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Strenuous physical training increases total blood volume (BV) through expansion of plasma volume (PV) and red cell volume (RCV). In contrast, exogenous erythropoietin (EPO) treatment increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO treatment on BV and markers of systemic and muscle iron homeostasis. In this longitudinal study, eight healthy nonanemic males were treated with EPO (50 IU/kg body mass, three times per week, sc) across 28 days of strenuous training (4 days/wk, exercise energy expenditures of 1,334 ± 24 kcal/day) while consuming a controlled, energy-balanced diet providing 39 ± 4 mg/day iron. Before (PRE) and after (POST) intervention, BV compartments were measured using carbon monoxide rebreathing, and markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Training + EPO increased (P < 0.01) RCV (13 ± 6%) and BV (5 ± 4%), whereas PV remained unchanged (P = 0.86). The expansion of RCV was accompanied by a large decrease in whole body iron stores, as indicated by decreased (P < 0.01) ferritin (-77 ± 10%) and hepcidin (-49 ± 23%) concentrations in plasma. Training + EPO decreased (P < 0.01) muscle protein abundance of ferritin (-25 ± 20%) and increased (P < 0.05) transferrin receptor (47 ± 56%). These novel findings illustrate that strenuous training combined with EPO results in both increased total oxygen-carrying capacity and hypervolemia in young healthy males. The decrease in plasma and muscle ferritin suggests that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole body and skeletal muscle iron stores.NEW & NOTEWORTHY Strenuous exercise training combined with erythropoietin (EPO) treatment increases blood volume, driven exclusively by red cell volume expansion. This hematological adaptation results in increased total oxygen-carrying capacity and hypervolemia. The marked upregulation of erythropoiesis with training + EPO reduces whole body iron stores and circulating hepcidin concentrations. The finding that the abundance of ferritin in muscle decreased after training + EPO suggests that muscle may release iron to support red blood cell production.

Patients with hypertension (HTN) are characterized by exaggerated vascular resistance and mean arterial pressure (MAP) and a compromised leg blood flow (Q_L) response to exercise recruiting a small muscle mass. However, the impact of hypertension on peripheral hemodynamics and the development of neuromuscular fatigue during locomotor activities, which critically depends on Q_L, remain unknown. Eight HTN (143 ± 11 mmHg/95 ± 6 mmHg; 45 ± 13 yr) and eight matched (age and activity) controls (120 ± 6 mmHg/77 ± 7 mmHg; CTRL) performed constant-load cycling exercise at 25, 50, and 75 W (for 4 min each) and at 165 ± 41 W (for 5 min). Exercise-induced locomotor muscle fatigue was quantified as the pre- to postexercise change in quadriceps twitch-torque (ΔQ_tw, peripheral fatigue) and voluntary activation (ΔVA%, central fatigue). Q_L (Doppler ultrasound) and leg vascular conductance (LVC) were determined during cycling at 25, 50, and 75 W. Heart rate and ventilatory responses were recorded during all intensities. MAP during exercise was, on average, ∼21 mmHg higher (P = 0.002) and LVC ∼39% lower (P = 0.001) in HTN compared with CTRL. Q_L was consistently between 20 and 30% lower (P = 0.004), and heart rate was significantly higher in HTN. Exercise-induced peripheral (ΔQ_tw: -53 ± 19% vs. -25 ± 23%) and central (ΔVA%: -7 ± 5% vs. -3 ± 2%) fatigue was significantly greater in HTN compared with CTRL. In addition to an exaggerated MAP, LVC and Q_L were lower during exercise in HTN compared with CTRL. Given the critical role of Q_L in determining the development of neuromuscular fatigue, these hemodynamic impairments likely accounted for the faster development of neuromuscular fatigue characterizing hypertensive individuals during locomotor exercise. NEW & NOTEWORTHY The impact of primary hypertension on the cardiovascular and neuromuscular fatigue response to locomotor exercise is unknown. We compared central and peripheral hemodynamics and the development of central and peripheral fatigue during cycling exercise in patients with stage I/II hypertension and age- and activity-matched healthy individuals. In addition to a significantly elevated blood pressure, hypertensive patients were, compared with their nonhypertensive counterparts, also characterized by considerable leg blood flow limitations and impaired neuromuscular fatigue resistance.