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

The extrinsic autonomic nervous system is critical in controlling most organ functions and is involved in the pathophysiology of many chronic diseases. However, its assessment plays a minor role in the clinical practice of diagnosis and treatment outside cardiology. Since sympathetic dysfunction is related to diseases such as diabetes, chronic stress, and urinary and gastrointestinal motor dysfunction, an autonomic assessment is warranted. Here, we evaluate the Baevsky Stress Index (SI) to assess sympathetic tone and reactivity based on heart rate variability. We start with discussing Baevsky's original stress index. We propose an optimized calculation of SI and assess the SI of 73 self-declared healthy subjects in the age groups 16-35, 35-50, and 50+ at supine baseline and in response to postural change from supine to standing. Normality assessment and kernel density analysis identified two subgroups: one we deemed to have normal autonomic functioning, and an outlier group with significantly higher baseline sympathetic index (SI) and sympathetic reactivity to standing. Using a Gaussian mixture model, we determined normal SI values and values for autonomic stress and autonomic dysfunction. This study provides a needed start to evaluate sympathetic dysfunction using heart rate variability.

The cause and consequences of inosine monophosphate (IMP) formation when adenosine triphosphate (ATP) declines during muscular contractions in vivo are not fully understood. The purpose of this study was to examine the role of IMP formation in the maintenance of the Gibbs free energy for ATP hydrolysis (ΔG_ATP) during dynamic contractions of increasing workload and the implications of ATP loss in vivo. Eight males (median 27.5, 25-35 yr range) completed an 8-min incremental protocol [2-min stages of isotonic knee extensions (0.5 Hz)] in a 3-T magnetic resonance (MR) system. Phosphorus MR spectra were obtained from the knee extensor muscles at rest and during contractions and recovery. Although the ATP demand during contractions was met primarily by oxidative phosphorylation, [ATP] decreased from 8.2 mM to 7.5 (range 6.4-8.0) mM and [IMP] increased from 0 mM to 0.6 (0.1-1.7) mM. Modeling showed that, in the absence of IMP formation, excess adenosine diphosphate (ADP) would result in a less favorable ΔG_ATP (P < 0.001). Neither [ATP] nor [IMP] had returned to baseline following 10 min of recovery (P < 0.001). Notably, Δ[ATP] was linearly related to the post-contraction reduction in muscle oxidative capacity (r = 0.74, P = 0.037). Our results highlight the importance of IMP formation in preserving cellular energy status by avoiding increases in ADP above that necessary to stimulate energy production pathways. However, the consequence of IMP formation was an incomplete recovery of [ATP], which in turn was related to decreased muscle oxidative capacity following contractions. These results likely have implications for the capacity to generate adequate energy during repeated bouts of muscular work.NEW & NOTEWORTHY An ∼9% decline in [ATP] led to the formation of inosine monophosphate (IMP) during submaximal muscular contractions. Modeling revealed IMP formed to preserve a favorable energy state (ΔG_ATP) by minimizing large increases in [ADP], whereas the loss of [ATP] did not alter ΔG_ATP. [ATP] did not recover by 10 min, and the loss of [ATP] was associated with a reduced oxidative capacity, providing a new link between [ATP] loss and an impaired energetic capacity in vivo.

The assessment of adrenergic modulation of sweating as assessed via pharmacologic administration of α- and β-adrenergic receptor blockers during exercise has yielded mixed findings. However, the underlying mechanisms for this disparity remain unresolved. We investigated the effects of separate and combined blockade of α- and β-adrenergic receptors on forearm sweating induced by a 30-min moderate-intensity exercise bout (n = 17, protocol 1) and the administration of adrenergic agonists epinephrine and norepinephrine (n = 16, protocol 2) in the heat. Adrenergic receptor blockade was induced via the separate and combined iontophoretic administration of terazosin (α-adrenergic receptor antagonist) and propranolol (β-adrenergic receptor antagonist) on forearm skin. Bretylium, a noradrenergic sympathetic nerve inhibitor, was also administered separately in protocol 1. In protocol 1, relative to the separate administration of propranolol, terazosin alone or in combination with propranolol attenuated exercise sweating to a similar extent (both P ≤ 0.037), although the effect was reduced relative to that observed with bretylium treatment (P < 0.001). In protocol 2, administration of propranolol increased norepinephrine- (P = 0.029) but not epinephrine-induced sweat rate. The combined administration of terazosin reversed this response, attenuating sweating (P < 0.001) to a greater extent than terazosin treatment alone (P = 0.030). Altogether, we showed that although β-adrenergic receptors may interact with α-adrenergic receptors pharmacologically, it does not appear to modulate exercise-induced sweating on the forearm. Furthermore, α- but not β-adrenergic receptors independently modulate the regulation of forearm sweating during exercise in the heat. Finally, the bretylium-induced reduction in forearm sweat rate during exercise likely occurs independently of α- and β-adrenergic receptors.NEW & NOTEWORTHY Pharmacological stimulation of α- and β-adrenergic receptors produces sweating in vivo. Still, the separate and interactive roles of these adrenergic receptors during exercise and pharmacological adrenergic stimulation in the heat remain unknown. We showed that β-adrenergic receptors may interact with α-adrenergic receptors pharmacologically, but it does not modulate exercise-induced sweating. The α-adrenergic receptors independently modulate sweating during exercise in the heat. We provide important new insights into our understanding of the mechanisms regulating human sweating.

Physical activity improves myocardial structure, function, and resilience via complex, incompletely defined mechanisms. We explored the effects of 1- to 2-wk swim training on cardiac and systemic phenotype in young male C57Bl/6 mice. Two-week forced swimming (90 min twice daily) resulted in cardiac hypertrophy (22% increase in heart:body weight, P < 0.01), with improved inotropy (22% higher left ventricular +dP/dt, P < 0.01) and functional tolerance to ischemia-reperfusion (I-R) (40%-50% reductions in stunning and diastolic dysfunction, P < 0.01; without changes in cell death assessed from enzyme loss) in Langendorff perfused hearts. Initial Western immunoblot analysis indicated no shifts in cardiac expression of determinants of autophagy (LC3A/B), mitochondrial biogenesis/dynamics (PGC-1α, MFN-1, and OPA-1), or stress signaling (caveolin-3 and GSK-3β). Furthermore, no changes in cardiac cytokines (IL-1b, IL-6, IL-10, IL-12, GM-CSF, TNF-α, and IFN-γ) were detected in multiplex immunoassays. Exploratory profiling of RTK phosphorylation provided evidence for moderately increased activity of receptors involved in cardiac/coronary growth and protection (insulin, IGF-1, FGF R2, Tie-2, PDGFβ, and EphB4), together with a fall in M-CSF R and ephrin sub-type receptor phosphorylation. Swimming increased growth factor while reducing inflammatory mediators across extracardiac tissues [brain, pancreas, thymus, lymph nodes, and white adipose tissue (WAT)]. This included a pattern of increased LIF, VEGF, and pentraxin-2 versus reduced CXCL2/MIP-2a, chitinase 3-like 1, CCL6, MMP9, CD40/TNFRSF5, and IGFBP6 in multiple tissues, and a shift to a pro-browning profile in WAT. In summary, swimming produces integrated systemic benefits, improving cardiac growth, inotropy, and resilience in association with increased growth factor and reduced inflammatory and lipogenic mediators in multiple tissues.NEW & NOTEWORTHY Swimming may induce cardiac and systemic benefits distinct from other modes of physical activity. We show that 2-wk forced swim training increases cardiac growth, contractility, and functional resilience to ischemia in hearts of male mice. This is associated with increased growth factor levels and reduced inflammatory and lipogenic protein profiles in peripheral tissues.

Obesity can change the immune microenvironment of adipose tissue and induce inflammation. This study is dedicated to exploring the internal mechanism by which different intensities of exercise reprogram the immune microenvironment of epididymal adipose tissue in nutritionally obese mice. C57BL/6J male obese mouse models were constructed by high-fat diet, which were respectively obese control group (OC), moderate-intensity continuous exercise group (HF-M), high-intensity continuous exercise group (HF-H), and high-intensity intermittent exercise group (HF-T). The exercise group was subjected to aerobic exercise intervention for 8 wk, and samples of mice were collected at the fourth and eighth week, respectively. Mice blood, liver, and adipose tissue of the epididymis were collected for index detection and adipose tissue ordinary transcriptome sequencing. After exercise intervention, when compared with the OC group, the morphology and blood indexes of the exercise groups were significantly improved. The liver lipid content was decreased, adipose tissue inflammation was reduced, and the mRNA and protein expression levels of IL-1β, F4/80, and CD64 in adipose tissue were significantly decreased (P < 0.01). Among the three exercise groups, the effect of the HF-T group was more significant. When compared with the OC group, fibroblast-specific marker genes, neutrophil marker genes, macrophage marker genes, and immune-related signaling pathways were significantly downregulated in the HF-T group. Exercise can reshape the immune microenvironment of adipose tissue, and high-intensity intermittent aerobic exercise is the most effective.NEW & NOTEWORTHY The present study has revealed that obesity is capable of altering the immune microenvironment within adipose tissue, thereby giving rise to inflammation. It has been demonstrated that exercise holds the potential to reverse the onset of inflammatory responses, with high-intensity intermittent aerobic exercise emerging as the most efficacious approach.

Nocturnal oxygen enrichment improves sleep at high altitudes but may impair acclimatization. Our purpose was to determine if nocturnal oxygen enrichment impacts acclimatization. A 7-day acclimatization protocol occurred at a field-based research site between 0 and 4,200 m. Participants were housed at 2,800 m and slept with ([Formula: see text], 32.3 ± 2.5% O₂) or without ([Formula: see text], 20.8 ± 0.1% O₂) nocturnal oxygen enrichment. Resting and steady-state cycling (5-min, 1.75 W·kg^-1) tests occurred on Day 0 (0 m) and Days 1, 4, and 7 (2,800 m). Sleep, vastus lateralis muscle oxygenation [oxygenated hemoglobin (O₂Hb), deoxygenated hemoglobin (HHb)], arterial blood oxygen saturation ([Formula: see text]), heart rate (HR), and expired gases were measured. Five daily hikes from 2,800 to 4,200 m were also completed. Sleep was longer (P = 0.028) and overnight [Formula: see text] higher (P < 0.001) in the [Formula: see text] (452 ± 63 min, 96 ± 1%) than the [Formula: see text] group (427 ± 63 min, 91 ± 2%). The [Formula: see text] and [Formula: see text] groups did not differ at rest in ΔO₂Hb (-1.47 ± 0.99, -1.46 ± 1.30 A.U., P = 0.901), ΔHHb (0.78 ± 0.84, 0.51 ± 0.96 A.U., P = 0.202), [Formula: see text] (93 ± 3, 93 ± 3%, P = 1.000), HR (59 ± 6, 64 ± 13 beats·min^-1, P = 0.229), respiratory exchange ratio (RER, 0.81 ± 0.07, 0.79 ± 0.06, P = 0.274), and ventilation body temperature pressure saturated (BTPS) (10.56 ± 2.12, 10.80 ± 1.96 L·min^-1, P = 0.717). The [Formula: see text] and [Formula: see text] groups also did not differ while cycling in ΔO₂Hb (-2.96 ± 3.03, -1.70 ± 3.46 A.U., P = 0.278), ΔHHb (7.59 ± 4.65, 6.34 ± 3.21 A.U., P = 0.451), [Formula: see text] (90 ± 6, 89 ± 6%, P = 0.875), HR (113 ± 10, 118 ± 16 beats·min^-1, P = 0.408), RER (0.89 ± 0.06, 0.89 ± 0.07, P = 0.756), and ventilation BTPS (54.00 ± 15.42, 60.18 ± 18.42 L·min^-1, P = 0.371). [Formula: see text] while cycling returned toward Day 0 (0 m) values by Day 7 (2,800 m) in both groups (P < 0.001) indicating short-term acclimatization. Nocturnal oxygen enrichment improves sleep but does not impair short-term acclimatization when completing daily prolonged exercise.NEW & NOTEWORTHY This work examined the impact of nocturnal oxygen enrichment on short-term high-altitude acclimatization to 2,800 m while completing daily hikes to 4,200 m. Recurrently dampening the required hypoxic stimulus for acclimatization via nocturnal oxygen enrichment improved sleep but did not impair short-term high-altitude acclimatization. This was evinced through ventilatory and cardiovascular adjustments that improved arterial blood oxygen saturation after 7 days.

The local sweat rate (LSR) response to intradermal electrical stimulation generates a sigmodal stimulus-response curve with a peak sweat rate generated during a 30-s period of continuous stimuli at a frequency of 16-32 Hz. However, the in vivo firing pattern of the sudomotor nerve resembles more of a bursting pattern. We tested the hypothesis that a bursting pattern during intradermal electrical stimulation would result in a greater sweating response than the regular continuous stimulus pattern. Fifteen subjects were studied in a temperature-controlled room at 27.6 ± 0.2°C. The LSR was measured with a miniature sweat capsule with guide sleeves for holding the intradermal stimulating electrodes. The nine continuous stimulus frequencies (0.2, 1, 2, 4, 8, 12, 16, 32, and 64 Hz) were compared to a bursting pattern with a similar total number of stimuli. The sweating response was determined as the area under the ∆LSR-time curve. Peak ∆LSR was slightly higher for the continuous stimuli (0.396 ± 0.242 mg·min^-1·cm^-2, P = 0.023) than for the bursting stimuli (0.356 ± 0.244 mg·min^-1·cm^-2). The sigmoidal-shaped stimulus-response curves, however, were significantly different (P = 0.0007). The stimulus frequency producing 50% of peak LSR (EC₅₀, P = 0.0029) was higher during continuous stimulation and the Hill slope was lower (P < 0.0001) during bursting stimuli. These data do not support the concept that a bursting stimulus pattern during intradermal electrical stimulation evokes a greater ∆LSR.NEW & NOTEWORTHY Neuron discharge variability can offer some advantages to a downstream physiological response. We examined this possibility with respect to sudomotor nerve activity and local sweat rate. Variable neuron discharge activity, induced by intradermal electrical stimulation, did not have an impact on the peak local sweat rate but did reduce the time to sweating onset and the stimulus intensity required to reach 50% of peak sweating (EC₅₀).

A previous study reported an increase in carotid-femoral pulse wave velocity (cfPWV) during an upright posture compared to the supine position, partly due to sympathetic activation. However, given that cfPWV is influenced by the transmural pressure (TMP) of the artery, which is elevated in the abdominal aorta in the seated posture due to the increased hydrostatic pressure. Thus, it remains unclear whether this increased cfPWV reflects a true rise in arterial stiffness or is simply a result of the elevated TMP. To assess the validity of cfPWV in the seated posture for arterial stiffness assessment, 20 young healthy subjects underwent arterial stiffness measurements in both the supine and seated positions. There were no significant differences in carotid artery compliance, β-stiffness index, and aortic characteristic impedance between the two positions (P = 0.209-0.380). However, cfPWV was higher in the seated posture than the supine posture (5.4 ± 0.6 vs. 6.2 ± 0.8 m/s, P < 0.0001), showing a high intraclass correlation coefficient (ICC) between positions (r = 0.841, P < 0.0001) and a parallel upward shift by 14% (y = 1.01x + 0.54). Moreover, cfPWV was correlated with TMP at the groin level (r = 0.532, P = 0.0004), and after adjusting for TMP at the groin level using analysis of covariance (ANCOVA), the posture-related difference in cfPWV was no longer significant (P = 0.867). These findings suggest that the increase in cfPWV observed in the seated posture is primarily due to elevated TMP caused by increased hydrostatic pressure, rather than a genuine rise in arterial stiffness. Consequently, cfPWV measurements taken in the seated posture may overestimate arterial stiffness unless they are appropriately adjusted for TMP.NEW & NOTEWORTHY This study demonstrated for the first time that the increase in carotid-femoral pulse wave velocity (cfPWV) observed in the seated posture is likely due to elevated transmural pressure (TMP) caused by increased hydrostatic pressure, rather than an actual rise in central arterial stiffness. Intraclass correlation analysis also showed a parallel upward shift in the regression line between supine and seated postures. This suggests that cfPWV values obtained in the seated position should be adjusted for hydrostatic pressure and TMP.

The organum vasculosum of the lamina terminalis (OVLT) is a forebrain circumventricular organ that modulates central autonomic control of arterial pressure and body fluid homeostasis. It has been implicated in the pathogenesis of rat models of hypertension that are driven by increased salt intake since OVLT lesion (OVLTx) attenuates both the DOCA-salt and angiotensin II-salt models. However, its contribution to the development of hypertension that is not salt-dependent, such as the 2 kidney, 1 clip (2K1C) renovascular model, is not clear. We recently reported that afferent renal denervation (ARDN) attenuates the pathogenesis of 2K1C hypertension in the rat and this was associated with a reduction of neurogenic pressor activity, water intake, vasopressin release, and renal inflammation, suggesting that afferent renal nerves, similar to OVLT, modulates central autonomic pathways that control arterial pressure and body fluid homeostasis. This idea led to the present study, which was designed to measure the effect of OVLTx on arterial pressure and body fluid homeostasis in 2K1C-HTN rats. Male Sprague-Dawley rats were randomly selected to receive OVLTx or sham operation and were instrumented 1 wk later with telemeters to continuously measure mean arterial pressure (MAP). The following week, rats received a silver clip around the left renal artery to generate 2K1C hypertension or sham-clip surgery. MAP was continuously measured for 6 wk, and once a week, rats were housed in metabolic cages for 24 h to evaluate water intake and urinary volume. Urine was analyzed for inflammatory cytokines and copeptin, a surrogate marker of vasopressin. Neurogenic pressor activity (NPA) was assessed on the last day of the protocol by measuring the peak MAP response to ganglionic blockade. Upon completion of the study, rats were euthanized and kidneys were removed for the measurement of inflammatory cytokine content. Hypertension in 2K1C rats was associated with increased NPA, water intake, vasopressin release, and renal inflammation. All of these responses were markedly attenuated or abolished in OVLTx 2K1C rats. These findings suggest that the OVLT, similar to afferent renal nerves, plays a key role in the development of hypertension, polydipsia, vasopressin release, and renal inflammation in 2K1C-HTN rats.NEW & NOTEWORTHY Renovascular hypertension (RVHT), accounting for 1%-5% of high blood pressure cases, is the most common secondary hypertension resistant to treatment. In two-kidney one-clip (2K1C) hypertensive rats, renal artery stenosis triggers sympathetic nervous system activation, increased vasopressin, water intake, and inflammation. OVLT lesions prevented these responses, similar to afferent renal denervation. This study suggests that OVLT plays a key role in 2K1C hypertension pathogenesis and interacts with afferent renal nerves. Future studies will explore the underlying mechanisms.

Dietary supplements are widely used among individuals exposed to hot environments, but whether their consumption confers any thermoregulatory effect is unclear. Therefore, we systematically evaluated the effect of dietary supplementation on key aspects of thermoregulation (core temperature [T_core] and sweating responses) in the heat. Three databases were searched in April 2024. After screening, 124 peer-reviewed articles were identified for inclusion within three separate meta-analyses: (1) peak T_core; (2) whole-body sweat rate (WBSR); (3) local sweat rate (LSR). The moderating effect of several variables (e.g. training and heat acclimation status), known to influence thermoregulatory function, were assessed via sub-analysis and meta-regression. There was no overall effect of the differing supplement types on WBSR (p = 0.405) and LSR (p = 0.769), despite taurine significantly increasing WBSR (n = 3, Hedges' g = 0.79, p = 0.006). Peak T_core was significantly affected by supplement type (p = 0.011), primarily due to caffeine's small significant positive effect (n = 30; Hedges' g = 0.44, p < 0.001) and taurine's (n = 3, Hedges' g = -0.66, p = 0.043) and oligonol's (n = 3; Hedges' g = -0.50, p = 0.014) medium significant negative effects. Dietary supplements, such as amino acids (e.g. taurine), some anti-oxidants and anti-inflammatories (e.g. oligonol) conferred the greatest thermoregulatory benefits during heat exposure. Taurine ingestion in such conditions may lower heat strain, which is likely through its augmentation of thermal sweating. Conversely, caffeine intake may potentially pose the greatest risk in the heat due to its effect on T_core.