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

Older adults have both lower pulmonary function and impaired thermoregulation compared with younger adults. In addition, epidemiological evidence suggests that extreme heat exposure increases the incidence of pulmonary complications in older adults. However, the impact of extreme heat exposure on pulmonary function in healthy older and younger adults is not well described. To assess this question, spirometry was performed at baseline in a thermoneutral environment and at the end of a 3-h heat exposure in a DRY (47°C and 15% humidity) and HUMID (41°C and 40% humidity) environment. Fifteen younger (7 female; 30 ± 5 yr) and 15 older (8 female; 72 ± 5 yr) adults completed the study. In the DRY condition, the younger adults had no change in forced vital capacity (FVC) from baseline (4.34 ± 0.55 L) to end-heating (4.31 ± 0.62 L; P = 0.72). In contrast, FVC in the older adults was increased from baseline (3.17 ± 0.72 L) to end-heating (3.29 ± 0.65 L; P = 0.02) in the DRY condition. Forced expiratory volume in 1 s (FEV₁) in the younger and older adults increased similarly from baseline (3.55 ± 0.47 and 2.38 ± 0.60 L, respectively) to end-heating (3.70 ± 0.50 and 2.51 ± 0.54 L, respectively; P = 0.003) in the DRY condition. The HUMID condition resulted in similar changes in FVC and FEV₁ in both age groups. In summary, the younger adults had an increase in expiratory airflow following heat exposure, indicative of some degree of bronchodilation, whereas the older adults had improved airflow in addition to increased FVC that could be indicative of altered pulmonary system compliance.NEW & NOTEWORTHY Pulmonary function increases in younger and older adults following 3 h of extreme heat exposure to a DRY (47°C and 15% humidity) and HUMID (41°C and 40% humidity) environment. Specifically, when hydration is maintained, FEV₁ increases as a result of heat-induced bronchodilation in both younger and older adults, whereas FVC increases in only the older adults due to potential improvements in pulmonary system compliance.

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), disrupts intestinal barrier function and alters gut microbiota composition, leading to systemic inflammation and metabolic disorders. To investigate the protective role of inulin in mitigating CIH-induced intestinal barrier dysfunction and systemic inflammation in mice, with a focus on the underlying gut microbiota-mediated mechanisms. C57BL/6J mice were exposed to CIH for 10 wk with or without inulin supplementation. Intestinal permeability, tight junction protein expression, inflammatory cytokine levels, and gut microbiota composition were assessed by FITC-Dextran assay, ELISA, RT-qPCR, Western blotting, hematoxylin-eosin staining, and 16S rRNA sequencing. The role of gut microbiota was evaluated using an antibiotic intervention. Inulin significantly reduced permeability of intestines, restored protein expression of tight junction, and alleviated histological damage. It lowered transforming growth factor-β, tumor necrosis factor-α, interleukin (IL)-23, -6, and 1β, IL-6 levels, whereas increasing IL-10. Inulin reversed CIH-induced gut dysbiosis, increased microbial diversity, and modulated the Firmicutes/Bacteroidetes ratio. Antibiotic treatment confirmed microbiota-dependent effects. Inulin mitigated dysfunction of intestinal barrier that was induced by CIH and systemic inflammation through modulation of gut microbiota, thus highlighting its potential as a dietary intervention for OSA-related complications.NEW & NOTEWORTHY Inulin alleviates intestinal barrier dysfunction caused by chronic intermittent hypoxia (CIH) in mice. By modulating gut microbiota, inulin reduces systemic inflammation, restores intestinal tight junction proteins, and improves gut health. This research highlights inulin's potential as a dietary intervention to mitigate complications related to obstructive sleep apnea and CIH-induced organ damage.

The pressure-generating capacity of the diaphragm is generally thought to be compromised at high lung volume either due to loss of curvature or loss of its membrane tension. At a state of hyperinflation during airway occlusion at total lung capacity, the diaphragmatic muscle is forced to contract from an initial shorter length, the zone of apposition narrows, insertional force on the chest wall is reduced, and abdominal compliance falls. We hypothesize that these altered mechanical conditions at high lung volume lead to a loss of the pressure-generating capacity that is mediated by excessive muscle shortening rather than loss of curvature of its muscle fibers. Using a biplane fluoroscopy, locations of radiopaque markers attached to the diaphragm muscle fibers and the lower three ribs of 10 beagle dogs weighing between 7 and 10.5 kg were determined. Such measurements were conducted during quiet spontaneous breathing and during forceful inspiratory efforts against an occluded airway at three lung volumes spanning the vital capacity from functional residual capacity (FRC) to total lung capacity (TLC). Our data show that transdiaphragmatic pressure (Pdi) at TLC was reduced by nearly 80% and surface area of the midcostal diaphragm muscle at contracted state during airway occlusion at TLC reduced by nearly 35% from its value at end of expiration. In addition, muscle fiber curvature was essentially maintained during the entire vital capacity of airway occlusion. Our data demonstrate that during airway occlusion at high lung volume, the pressure-generating capacity of the diaphragm is compromised primarily due to a mechanism that involved a combined mechanical effect of hyperinflation and excessive muscle contraction rather than a significant loss of curvature of its muscle fibers.NEW & NOTEWORTHY Data from the current study support the hypothesis that the pressure-generating capacity of the diaphragm at high lung volume is compromised primarily due to a mechanism that involves a combined mechanical effect of hyperinflation and substantial muscle contraction rather than a significant loss of its muscle fiber curvature.

Pregnancies affected with placental insufficiency and fetal growth restriction (FGR) are characterized by reduced umbilical blood flow, decreased nutrient and oxygen supply to the fetus, and impaired fetal skeletal muscle growth. Vascular development within FGR skeletal muscle has not been well described. We hypothesized that chronic placental insufficiency impairs microvascular architecture in FGR fetal skeletal muscle, resulting in decreased vascularity. We used a sheep model of placental insufficiency-induced FGR by exposing pregnant ewes to elevated temperature. Four muscles from the hindlimb were obtained in late gestation from FGR and control fetal sheep for histological and molecular analyses. The proportion of slow-twitch oxidative fibers was 22% lower in the tibialis anterior (TA) and 32% lower in the extensor digitorum longus (EDL) muscles in FGR fetuses compared with controls. Total cross-sectional area was 20%-45% lower in biceps femoris (BF), TA, EDL, and soleus (SOL) muscles. The capillary number per myofiber was 34% lower in BF, 51% lower in TA, and 21% lower in SOL FGR muscles compared with controls. Capillary area was also 44% lower in the FGR TA muscle. Taken together, late gestation fetuses with placental insufficiency-induced FGR had smaller myofibers, fewer slow-twitch oxidative myofibers, and defects in angiogenesis and capillary formation.NEW & NOTEWORTHY Pregnancies affected by placental insufficiency-induced FGR result in fewer slow-twitch oxidative myofibers and lower capillary number per myofiber in fetal skeletal muscle by late gestation.

Exposure to an elevated state of hyperthermia is associated with heat-induced cytotoxicity, which, if left unabated, can cause tissue damage and death. Although activation of autophagy is vital to counter heat-induced cellular injury and promote cellular survival, the dose-dependent autophagic response to controlled elevations in body core temperature has yet to be evaluated in an in vivo human model. Therefore, on separate days, we evaluated cellular responses in 12 young adults [means (SD): 22 (2) yr; 6 women] who were immersed (up to the clavicle) in water set at a temperature to clamp core temperature (esophageal) at either baseline resting (control; 37°C), warm (38°C), or hot (39°C) conditions for 60 min. Autophagy was characterized in peripheral blood mononuclear cells before and after water immersion, as well as following 3 h of seated recovery in a temperate environment (∼22°C). Proteins associated with autophagy and cellular stress pathways (apoptosis, inflammation, and heat shock response) were assessed via Western blot. With increasing levels of hyperthermia, we observed increasing autophagic activation (as indexed via elevated LC3-II and decreasing p62) at end exposure to warm and hot core temperature clamps, with evidence of elevated autophagic activity up to 3 h after exposure to the hot condition. This was paired with significant end exposure elevations in cellular stress proteins including cleaved-caspase-3, TNF-α, and IL-6 in the hottest condition. Taken together, our findings suggest that autophagy is activated with increasing levels of hyperthermia and may be important in restoring cellular homeostasis when exposed to body core temperatures above 38°C in healthy young adults.NEW & NOTEWORTHY Our findings suggest that autophagic regulation is stimulated in peripheral blood mononuclear cells associated with elevations in body core temperature induced through warm-to-hot water immersion. Importantly, our findings propose that autophagy may be important in restoring cellular homeostasis when exposed to body core temperatures above 38°C in healthy young adults. Therefore, the use of warm-to-hot water immersion may provide a potent model to study cellular heat stress responses in humans.

The morphology of the larynx is essential for vocalization, respiration, and airway protection, yet the sources of phenotypic variation within species are not well understood. This study investigated whether genetic background exerts a stronger influence than environmental factors on laryngeal morphology in two house mouse strains. Using geometric morphometrics, we analyzed the size and shape of 79 laryngeal specimens and examined the effects of body size, genetics, obesity, exercise, and social housing. Our results demonstrate that genetic background significantly shapes laryngeal structure. There were significant shape differences between the two genetic strains, and the inbred strain showed less phenotypic variation than the outbred mice. Although these structural differences likely arose without direct selection, they were associated with marginal differences in vocal output, suggesting functional relevance. Obesity and exercise also influenced laryngeal morphology, but their effects were secondary to genetics. Notably, leptin levels were linked to size and shape changes in the vocal organ. These findings suggest that random genetic drift and pleiotropy can be important drivers of laryngeal evolution in house mice. Overall, both genetic and environmental factors contribute to laryngeal shape, underscoring the organ's plasticity.NEW & NOTEWORTHY How are voice, swallowing, and breathing shaped by genes, environment, and diet? This study in house mice shows that genetic background, obesity, exercise, and social housing all influence laryngeal structure and function. Laryngeal shape seems to be affected by pleiotropy and genetic drift. Outbred mice show greater variation than inbred ones, and leptin-deficient mice have smaller vocal organs-highlighting the larynx as a dynamic, responsive structure shaped by multiple forces.

Strenuous physical work in hot environments can impair kidney function and potentially cause acute kidney injury (AKI). Heat acclimation is recommended to reduce thermal strain but its efficacy in mitigating decrements in kidney function remains unclear. The present study tested the hypothesis that 10 days of heat acclimation attenuates increases in serum creatinine (ΔCr) during exercise heat stress. Twenty healthy adults (14 females) completed 10 days of fixed-intensity treadmill walking for 120 min in a climatic chamber (40°C) to induce heat acclimation. Kidney function was assessed as ΔCr from pre-to-post exercise on days 1 (D1) and 10 (D10). Plasma neutrophil gelatinase-associated lipocalin (ΔNGAL) was measured to estimate the magnitude of renal ischemia. The increase in core temperature (Tc) from pre- to postexercise was attenuated on D10 (Post: 38.3 ± 0.4°C) compared with D1 (Post: 38.8 ± 0.5°C, P < 0.001). Heat acclimation did not alter the increase in ΔCr and ΔNGAL to exercise heat stress (P ≥ 0.325). There was a strong correlation between ΔTc and ΔCr on D10 (r = 0.61) but no correlation on D1 (P = 0.908). There was no correlation between ΔTc and ΔNGAL on either day (P ≥ 0.480). There was a strong correlation between ΔNGAL and ΔCr on D1 (r = 0.694) but no correlation on D10 (P = 0.118). These findings indicate that heat acclimation does not alter the magnitude of increase in circulating biomarkers of kidney function following exercise heat stress. However, that ΔCr was correlated with ΔTc on D10 but not on D1 suggests that the kidneys may exhibit increased sensitivity to hyperthermia in heat-acclimated individuals.NEW & NOTEWORTHY Heat acclimation provides beneficial adaptation during heat stress. The impact of heat acclimation on kidney function are not well understood. This short report provides findings that plasma neutrophil gelatinase-associated lipocalin (NGAL) and creatinine appear to be unaffected by acute heat stress before and after heat acclimation, but that the kidneys may exhibit increased sensitivity to hyperthermia in heat-acclimated individuals.

Major depressive disorder (MDD) often first emerges during young adulthood and is associated with an increased risk of future hypertension, but our understanding of blood pressure (BP) regulation in young adults with MDD who are otherwise clinically healthy remains limited. We tested the hypothesis that beat-to-beat BP variability (BPV) would be greater in young unmedicated adults with MDD compared with nondepressed healthy adults (HA). Because the arterial baroreflex is essential for beat-to-beat BP regulation, we also hypothesized that 1) sympathetic baroreflex sensitivity would be reduced in young adults with MDD and 2) positively related to BPV. Beat-to-beat BP (finger photoplethysmography), heart rate (ECG), and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were measured during 10-20 min of supine rest in 40 young adults with MDD (unmedicated; n = 19 females) and 27 HA (n = 17 females). There were no group differences in either resting BP (116 ± 10/73 ± 6 HA vs. 113 ± 9/74 ± 6 mmHg MDD; both P > 0.05) or MSNA (26 ± 11 vs. 24 ± 13 bursts/100 heartbeats MDD; P = 0.50). Neither beat-to-beat BPV (e.g., systolic BP standard deviation: 5.8 ± 2.1 HA vs. 5.9 ± 1.6 mmHg MDD, P = 0.47) nor sympathetic baroreflex sensitivity (e.g., burst incidence gain: -3.8 ± 1.3 HA vs. -3.4 ± 1.5 bursts/100 beats/mmHg MDD, P = 0.34) was different in MDD compared to HA. In adults with MDD, sympathetic baroreflex sensitivity was related to BPV (r = 0.52, P = 0.01). Traditional measures of beat-to-beat cardiac output and total peripheral resistance variability were likewise not different between groups (all P > 0.05). These data demonstrate that both beat-to-beat BPV and sympathetic baroreflex sensitivity are preserved in young unmedicated adults suffering from MDD.NEW & NOTEWORTHY This study investigated beat-to-beat blood pressure variability (BPV) in young unmedicated adults with major depressive disorder (MDD). The results demonstrated that both BPV and sympathetic baroreflex sensitivity were preserved in young unmedicated adults with MDD compared with healthy nondepressed young adults.