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

Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. METHODS: Plasma ET-1 was quantified in 60 men categorized as young (N=20, age=30±4 y, testosterone=510±63 ng/dL), middle-aged/older with normal testosterone (N=20, age=59±6 y, testosterone=512±115 ng/dL), or middle-aged/older with low testosterone (N=20, age=60±8 y, testosterone=265±47 ng/dL). Endothelial function was determined via FMD. Venous and arterial endothelial cells were harvested in a subset of participants and stained for ET-1 expression. RESULTS: Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7±2.2%) compared to young men (7.3±1.3%, p=0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0±1.8%, p=0.010 vs, middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6±0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0±1.4 ng/dL p=0.681) but was higher in middle-aged/older men with low testosterone (7.7±2.8 ng/dL) compared to both groups (p<0.001 vs. young men; p=0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous (p=0.616) or arterial (p=0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD (r=-0.371, p=0.004). CONCLUSIONS: These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1.

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.

Hypoxia at high altitude can constrain aerobic metabolism and elicit physiological responses that are detrimental to health and fitness. Responses of the sympathoadrenal system are vital for coping with acute hypoxia, but can become maladaptive with prolonged activation in chronic hypoxia. We examined how adrenal function is altered in high-altitude populations of deer mice (Peromyscus maniculatus), which have evolved to overcome chronic hypoxia in their native environment. High- and low-altitude populations were each born and raised in common lab conditions, and then acclimated to normoxia or chronic hypoxia during adulthood. High-altitude mice exhibited lower plasma epinephrine concentrations than low-altitude mice in both normoxia and hypoxia. Primary cultures of chromaffin cells were used to examine the cellular mechanisms underlying differences in epinephrine secretion from the adrenal medulla. Chromaffin cells from high-altitude mice did not mount a diminished Ca²⁺ response to nicotinic stimulation, but cellular catecholamine stores were much lower in high-altitude mice than in low-altitude mice. Histological analyses of the adrenal gland showed that high-altitude mice did not have smaller adrenal medullae. Therefore, reductions in chromaffin cell catecholamine stores were the primary mechanism for lower secretion rates and circulating concentrations of catecholamines in high-altitude mice, which may help avoid sympathoadrenal over-activity in chronic hypoxia. Further exploratory analysis found that high-altitude mice have a larger adrenal cortex and higher plasma concentrations of corticosterone, which could reflect changes in stress responsiveness or metabolic regulation. Therefore, multiple evolved changes in the physiology of the adrenal gland may contribute to high-altitude adaptation in deer mice.

Background: Vitamin D is associated with sleep quality and duration, but it's unclear whether vitamin D status influences sleep variability. Therefore, we sought to determine whether vitamin D status was associated with sleep variability in healthy adults. Methods: We assessed objective sleep, including timing and duration standard deviation (SD) using the Philips Actiwatch Spectrum and subjective sleep quality using the Pittsburgh Sleep Quality Index (PSQI) in 130 adults. We measured plasma 25(OH)D concentration to assess vitamin D. We used one-way ANOVAs and Kruskal-Wallis tests to compare sleep in participants characterized as vitamin D deficient (<20ng/mL), insufficient (21-29ng/mL), and sufficient (>30ng/mL). We used covariate-adjusted linear regression to assess associations between vitamin D status and sleep metrics. We compared differences in 'low' and 'high' sleep variability based on vitamin D status using Chi-Squared test. Results: There was an effect of vitamin D status on sleep timing SD (Kruskal-Wallis, p=0.021) and sleep duration SD (Kruskal-Wallis, p<0.001). There was an inverse association between vitamin D status with sleep duration SD (after covariate adjustment R²=0.267, p<0.001, deficient vs. sufficient p=0.050, insufficient vs. sufficient p=0.022). There was no effect of vitamin D status on objective sleep duration, efficiency, or PSQI scores (ps>0.05). We did not observe differences in 'low' and 'high' sleep timing SD based on vitamin D status (²=5.43, p=0.066), but we did for sleep duration SD (²=22.4, p<0.001). Conclusion: Our data indicate that individuals with poor vitamin D status exhibit greater objective sleep variability.

Background: We aimed to explore the role of Amino acid metabolism (AAM) and identify biomarkers for prognosis management and treatment of lung adenocarcinoma. Methods: Differentially expressed genes (DEGs) associated with AAM in lung adenocarcinoma were selected from public databases. Samples were clustered into varying subtypes using ConsensusClusterPlus based on gene levels. Survival analysis was conducted using a survival package, and immune analysis was performed using ssGSEA and ESTIMATE. Enrichment analysis was performed using GSEA, and a protein-protein interaction network of DEGs between subgroups was established through STRING. Hub genes were screened and verified using survival analysis, and drug sensitivity prediction was performed. Results: 163 DEGs associated with AAM in lung adenocarcinoma were obtained, and two AAM-associated subtypes were identified. Cluster1 showed higher survival rates and immune levels compared with cluster2. The two subtypes were mainly enriched in immune-related signaling pathways such as B cell receptor, Jak-Stat, and natural killer cell-mediated cytotoxicity. Additionally, the mutation landscape between the two groups was significantly different. F2, AHSG, and APOA1 were key hub genes that significantly affected the prognosis differences between the two subtypes. Cluster2 showed higher sensitivity to drugs such as Mithramycin, Depsipeptide, and Actinomycin than cluster1. Conclusion: This study identified two AAM-associated gene subtypes and their biomarkers and predicted the immune status and drug treatment sensitivity of varying subtypes. The results are instructive in the clinical treatment of lung adenocarcinoma.

There have been few studies that have examined hemodynamic responses to low-frequency neuromuscular electrical stimulation (LF-NMES), and the effects of combining passive cycle ergometry are still unclear. The purpose of this study was to examine the effects of a combination of LF-NMES and passive cycle ergometry on hemodynamic responses with a primary focus on the Fick principle in healthy adults. A randomized, crossover trial was conducted to evaluate the responses to three types of supine exercises (LF-NMES alone, LF-NMES with passive cycle ergometry, and voluntary cycle ergometry) adjusted to the same exercise intensity as the oxygen consumption of 14 mL/kg/min in 13 healthy adult men. Blood pressure, heart rate, blood lactate concentration, stroke volume (SV), cardiac output (CO), and left ventricular end-diastolic volume (LVEDV) were measured during each exercise in all subjects. The arterial-venous oxygenation difference (A-V̇o₂ difference) was calculated based on Fick's equation. LVEDV, SV, and CO were lower, and the A-V̇o₂ difference and blood lactate concentration were higher in LF-NMES alone than those in voluntary cycle ergometry and LF-NMES with passive cycle ergometry (P < 0.05). The blood lactate concentration was lower in LF-NMES with passive cycle ergometry than that in LF-NMES alone, but slightly higher than that in voluntary cycle ergometry (P < 0.05). Hemodynamic and metabolic responses of exercise with LF-NMES alone seemed consistent with insufficient peripheral perfusion based on the elevation of A-V̇o₂ difference and blood lactate concentration. The findings suggest that combining passive cycle ergometry with LF-NMES improves the insufficient peripheral perfusion induced by LF-NMES alone.NEW & NOTEWORTHY This is the first study to evaluate cardiac output, oxygen consumption, and A-V̇o₂ difference during LF-NMES of endurance exercise modality. LF-NMES alone may not demonstrate hemodynamic responses induced by voluntary endurance exercise, however, demonstrates those when combined with passive cycle ergometry. LF-NMES with passive cycle ergometry may be a more effective approach in cardiac rehabilitation for patients without the ability of voluntary exercise because it may increase cardiac output and venous return as represented by the LVEDV.

Marine teleosts experience ion gain and water loss in their natural habitats. Among other tissues, the urinary bladder epithelium of marine fishes has been shown to actively transport ions to facilitate water absorption. However, transport properties of the urinary bladder epithelium of marine fishes and its plasticity in altered ambient salinities is relatively under-investigated. We describe urinary bladder epithelium electrophysiology, water flux, and expressions of ion transporters in urinary bladder tissue of Gulf toadfish (Opsanus beta) acclimated to either 35 ppt or 60 ppt seawater. Water absorption in bladder sac preparations increased ∼350% upon acclimation to 60 ppt. Increases in water transport coincided with a significant ∼137% increase in urinary bladder tissue mucosal-to-serosal short circuit current (I_sc) and a ∼56% decrease in tissue membrane resistance. Collectively, these metrics indicate that an active electrogenic system facilitates water absorption via Na⁺ (and Cl^-) transport in urinary bladder tissue. Furthermore, pharmacological inhibition of urinary bladder tissue I_sc and expression of a suite of ion transporters and channels previously unidentified in this tissue provide mechanistic insights into the transport processes responsible for water flux. Analysis of water transport to overall Gulf toadfish water balance reveals a modest water conservation role for the urinary bladder of ∼0.5% of total water absorption in 35 ppt and 1.9% in 60 ppt acclimated toadfish. These results emphasize that electrogenic ion transport facilitates water-absorptive properties of the urinary bladder in Gulf toadfish-a process that is regulated to facilitate water homeostasis.NEW & NOTEWORTHY Novel experiments showcasing increased urinary bladder water absorption, ion transport, and altered channel/transporter expression in a marine fish acclimated to high salinities. Our results provide additional and noteworthy mechanistic insight into the ionoregulatory processes controlling water transport at the level of the urinary bladder in marine teleosts. Experimental outcomes are applied to whole organism-level water transport values, and the relative importance of marine teleost urinary bladder function to overall organism water conservatory measures is discussed.

Adaptations to skeletal muscle following resistance exercise are due in part to changes to the skeletal muscle transcriptome. Although transcriptional changes in response to resistance exercise occur in young and aged muscles, 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 exercises in humans. However, the extent to which unilateral eccentric contractions in young and aged rodents mimic the transcriptional response in humans remains unknown. We reanalyzed 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 in 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.NEW & NOTEWORTHY Acute eccentric muscle contractions in rodents are used to model resistance exercise in young and aged humans, including changes to the muscle transcriptome. This work defines the utility of the rodent model at mimicking the transcriptional features observed in young and aged humans.

Age and sex may alter the cerebral blood flow (CBF) responses to acute isometric exercise, via associated elevations in mean arterial pressure (MAP) and sympathetic activation. Our aim was to determine the relationships between age, sex, and exercise intensity on cerebrovascular responses to isometric handgrip exercise. In 78 healthy adults (18-80 yr, n = 42 females), cerebrovascular responses were assessed during 2-min isometric exercise bouts at three intensities [15, 30, 45% maximal voluntary contraction (MVC)]. Intracranial responses of the middle cerebral artery (MCA) and posterior cerebral artery (PCA) velocity (v) were measured using transcranial Doppler ultrasound. Extracranial responses of the internal carotid artery (ICA) and vertebral artery (VA) were assessed using Duplex ultrasound. Cardiopulmonary hemodynamic and neural parameters were measured throughout, including muscle sympathetic nerve activity, end-tidal carbon dioxide, and MAP. There were significant positive relationships between exercise intensity and the cerebral responses of the MCAv (P < 0.001) and PCAv (P = 0.005). There were no effects of intensity on ICA and VA responses (P > 0.05), despite intensity-dependent increases in MAP (P < 0.001). The increased MCAv response to exercise was blunted with advancing age (P = 0.01) with no influence of sex (P = 0.86). The present study provides data on age, sex, and intensity-specific relationships with intracranial and extracranial cerebrovascular responses to isometric exercise. Despite similar ICA, VA, and PCA responses, MCAv responses were attenuated with advancing age during handgrip exercise with no sex-dependent influence. Furthermore, intracranial responses were intensity dependent, whereas extracranial blood flow, shear-stress, and velocity responses were similarly increased at all intensities during handgrip exercise.NEW & NOTEWORTHY The influence of aging and sex on cerebral blood flow responses to isometric exercise are unknown. We observed intensity-dependent increases in velocity of the intracranial arteries, whereas the extracranial artery responses were similarly increased at all intensities during handgrip exercise in young and older individuals. Furthermore, we observed a blunted middle cerebral artery velocity response to handgrip exercise with advancing age, whereas the posterior circulation and extracranial responses were preserved across the lifespan in healthy individuals in males and females alike.