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

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 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).

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.

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 weeks, and samples of mice were collected at the 4th and 8th 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 down-regulated in the HF-T group. Exercise can reshape the immune microenvironment of adipose tissue, and high-intensity intermittent aerobic exercise is the most effective.

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.

Dehydration, characterized by the loss of total body water and/or electrolytes due to diseases or inadequate fluid intake, is prevalent globally but often underestimated. Its contribution to long-term chronic diseases and sarcopenia is recognized, yet the mechanisms involved in systemic and muscle protein metabolism during dehydration remain unclear. This study investigated metabolic adaptations in a 36-h water deprivation (WD) model of mice. Male C57BL/6 mice underwent 36-h WD or pair-feeding at rest, with assessments of motor skills along with biochemical and metabolic parameters. Dehydration was confirmed by hypernatremia, body mass loss, hyporexia, and increased activity of vasopressinergic and oxytocinergic neurons compared with controls. These results were associated with liver mass loss, decreased glycemia, and increased cholesterolemia. In addition, increased V̇o₂ and a decreased respiratory exchange ratio indicated reduced carbohydrate consumption and potentially increased protein use during dehydration. Thus, skeletal muscle protein metabolism was evaluated due to its high protein content. In the oxidative muscles of the WD group, total and proteasomal proteolysis increased, which was associated with decreased Akt-mediated intracellular signaling. Interestingly, there was an increase in fiber cross-sectional area, likely due to higher muscle water content caused by increased intracellular osmolality induced by protein catabolism products. Conversely, no changes were observed in protein turnover or water content in glycolytic muscles. These findings suggest that short-term WD imposes a procatabolic state, depleting protein content in skeletal muscle. However, skeletal muscle may respond differently to dehydration based on its phenotype and might adapt for a limited time.NEW & NOTEWORTHY This study investigated the effects of WD on mouse homeostasis, focusing on energy substrates and skeletal muscle protein metabolism. Our findings revealed a shift toward reduced dependence on carbohydrate degradation and increased reliance on lipid oxidation, or even protein oxidation, as energy sources, since we observed increased proteolysis in one muscle phenotype. Despite body mass loss, soleus and EDL muscle masses were differently affected. These results indicate the procatabolic potential of short-term WD in mice.