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.

A burst of muscle sympathetic nerve activity (MSNA) induces vasoconstriction that transiently reduces regional vascular conductance and increases systemic blood pressure (BP) over the subsequent 4-8 cardiac cycles. These responses are termed sympathetic neurovascular transduction and sympathetic transduction of BP, respectively. Sympathetic transduction of BP is commonly calculated and interpreted as a proxy measure for regional sympathetic neurovascular transduction despite the systemic nature of BP regulation. The present analysis tested whether the peak change in signal-averaged sympathetic transduction of BP was correlated to the change in regional sympathetic vascular transduction at rest. Fourteen adults (5 females, 23 ± 3 yr) arrived at the laboratory, ate a standardized meal, and rested for 90-120 min. MSNA (fibular nerve microneurography), heart rate (electrocardiography), beat-to-beat BP (finger photoplethysmography), and superficial femoral artery blood flow (Doppler ultrasound) were obtained continuously for 10 min in the supine position. Femoral vascular conductance (FVC) was calculated as blood flow divided by mean arterial BP. The peak change in diastolic BP following a burst of MSNA was correlated to the corresponding nadir change in femoral vascular conductance (r = -0.58 [-0.07 to -0.85], P = 0.03) and superficial femoral artery blood flow (r = -0.54 [-0.17 to -0.83], P = 0.04). The nadir change in diastolic BP in cardiac cycles not following an MSNA burst was correlated to the peak change in femoral vascular conductance (r = -0.42 [-0.83 to 0.00], P = 0.05), but not superficial femoral artery blood flow (r = 0.41 [-0.77 to 0.15], P = 0.14). In conclusion, more commonly assessed sympathetic transduction of BP provides moderate insight into regional sympathetic neurovascular transduction.NEW & NOTEWORTHY The majority of studies have used signal-averaged sympathetic transduction of blood pressure as a generalized measure of transduction. In this analysis, we show that sympathetic transduction of blood pressure and regional sympathetic vascular transduction were moderately correlated in healthy adults at rest. The moderate strength of this relationship highlights potential differences between regional and systemic assessments of sympathetic transduction and suggests that future work should choose the transduction measure best aligned with the research question.

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.

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.

Preterm birth increases the risk of cardiometabolic disease in adulthood. Infants born during the second trimester of pregnancy, a critical period of hypothalamic development, are at risk of sodium (Na) depletion due to renal immaturity and large urine Na losses. We previously demonstrated in male mice that Na restriction during the equivalent mouse hypothalamic development period (PD21-PD42) programs long-term changes in energy balance via increased thermogenic sympathetic nervous activity. We therefore hypothesized that early-life Na restriction programs changes in cardiovascular control via altered autonomic activity. C57BL/6J male mice were supplied a low (0.04%) Na or supplemented (0.30%) Na diet from PD21-PD42, before return to standard (0.15%) Na diet. Hemodynamic and autonomic functions were assessed by radiotelemetry and acute administration of autonomic antagonists before and after all animals were switched to a high Na diet (HSD; 1% Na) at 12 weeks of age. Mice were additionally treated with the angiotensin II type 1 receptor (AT₁R) antagonist, losartan, for two weeks. On standard diet, early-life Na restriction resulted in small but significantly different hemodynamic responses to autonomic blockers without effect on systolic blood pressure (SBP) or heart rate (HR). HSD increased SBP in 0.04% but not 0.30% Na mice, accompanied by increased cardiac sympathetic activity. Losartan had a greater BP lowering effect in early life Na-restricted mice. Our findings suggest Na restriction during a critical hypothalamic developmental period programs long-term changes in autonomic control of cardiovascular functions and may offer insight into the increased risk of cardiovascular disease in former preterm infants.

Vagal sensory afferents carrying information from the gastrointestinal tract (GI) terminate in the nucleus of the solitary tract (NTS). Different subpopulations of NTS neurons then relay this information throughout the brain. Cholecystokinin (CCK) is a satiety peptide that activates vagal afferents in the GI. However, CCK is also expressed by neurons in the NTS, and activation of these neurons decreases food intake. What is less clear is how these NTS CCK neurons are activated by vagal afferents and what type of information they integrate about meal size and content. To address this, we identified NTS-CCK neurons by crossing CCK-IRES-Cre mice with floxed-Rosa-tdtomato mice and made a horizontal brain slice containing vagal afferents in the solitary tract (ST). Voltage clamp recordings of NTS-CCK neurons show that activation of the ST evokes excitatory post-synaptic currents (EPSCs) mediated by both AMPA and NMDA receptors. Analysis of these EPSCs revealed that 80% of NTS-CCK neurons receive direct, monosynaptic inputs, with many also receiving indirect, or polysynaptic, inputs. NTS-CCK neurons are sensitive to the TRPV1 agonist capsaicin, suggesting they are downstream of C-fibers. In addition, both CCK and a 5-HT3R agonist increased sEPSC frequency in NTS-CCK neurons, with 69% of NTS-CCK neurons sensitive to CCK and 42% to 5-HT3 receptor agonists, as well as 45% sensitive to both and 10% to neither. Taken together with previous studies, this suggests that NTS-CCK neurons are driven primarily by vagal afferents that are sensitive to CCK and are only weakly driven by those sensitive to 5-HT.

Adaptations to skeletal muscle following resistance exercise are due in part to changes to the skeletal muscle transcriptome. While transcriptional changes in response to resistance exercise occur in young and aged muscle, aging alters this response. Rodent models have served great utility in defining regulatory factors that underscore the influence of mechanical load and aging on changes to skeletal muscle phenotype. Unilateral eccentric contractions in young and aged rodents are widely used to model resistance exercise in humans. However, the extent to which unilateral eccentric contractions in young and aged rodents mimics the transcriptional response in humans remains unknown. We re-analyzed two publicly available RNA sequencing datasets from young and aged mice and humans that were subjected to acute eccentric contractions to define key similarities and differences to the muscle transcriptional response following this exercise modality. The effect of aging on the number of contraction-sensitive genes, the distribution patterns of those genes into unique/common categories, and the cellular pathways associated with the differentially expressed genes (DEGs) were similar in mice and humans. However, there was little overlap between species when comparing specific contraction-sensitive DEGs within the same age group. There were strong intraspecies relationships for the common transcription factors predicted to influence the contraction-sensitive gene sets, whereas interspecies relationships were weak. Overall, these data demonstrate key similarities between mice and humans for the contraction-induced changes to the muscle transcriptome, but we posit species-specific responses exist and should be taken into consideration when attempting to translate rodent eccentric exercise models.

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℃) 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. Additionally, 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.

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).