Physiological Reports最新文献

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The purpose of this study was to determine the effect of hydration status on the change in sweat sodium (Na⁺), chloride (Cl^-), and potassium (K⁺) concentrations during exercise-heat stress. Fifteen subjects (Six female, nine male; 29 ± 9 y; 71 ± 14 kg) completed 90 min of cycling (81% HR_max) in the heat (~33°C, 42% rh) with fluid replacement to maintain euhydration (EUH) or without fluid to dehydrate to 2.4 ± 0.4% body mass loss (DEH). Sweat was collected from the forehead (FH), right scapula (SCAP), and left (LVFA) and right (RVFA) ventral forearms using the absorbent pad technique at the beginning (0-30 min) and end of exercise (60-90 min). Sweat was analyzed for Na⁺, Cl^-, and K⁺ concentrations using ion chromatography. Data are reported as mean ± SD or median ± IQR. There were no differences (Paired t-tests or Wilcoxon signed-rank tests) between EUH and DEH in the change in sweat Na⁺ (FH: 24.3 ± 21.5 vs. 30.8 ± 22.4 mmol/L; SCAP: 9.7 ± 6.2 vs. 9.6 ± 8.2 mmol/L; LVFA: 7.5 ± 6.0 vs. 5.6 ± 5.9 mmol/L; RVFA: 8.2 ± 8.6 vs. 7.8 ± 5.2 mmol/L), sweat Cl^-, or sweat K⁺ at any site (p = 0.07-0.99). The change in sweat electrolyte concentrations during 90 min of exercise in the heat was not significantly influenced by mild dehydration in recreational to moderately-trained male and female athletes.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. DKD is a heterogeneous disease with complex pathophysiology where early endothelial dysfunction is associated with disease progression. The Tie2 receptor and Angiopoietin 1 and 2 ligands are critical for maintaining endothelial cell permeability and integrity. Tie2 signaling is negatively regulated by the endothelial specific transmembrane receptor Vascular Endothelial Protein Tyrosine Phosphatase (VEPTP). Genetic deletion of VEPTP protects from hypertension and diabetes induced renal injury in a mouse model of DKD. Here, we show that VEPTP inhibition with an extracellular domain targeting VEPTP antibody induced Tie2 phosphorylation and improved VEGF-A induced vascular permeability both in vitro and in vivo. Treatment with the VEPTP blocking antibody decreased the renal expression of endothelial activation markers (Angpt2, Edn1, and Icam1) but failed to improve kidney function in db/db uninephrectomized ReninAAV DKD mice.

This study assessed the impact of sweetened alcohol and naringin on cardiac function in Sprague-Dawley rats. Male (n = 40) and female (n = 40) rats were allocated to control, sweetened alcohol (SOH), naringin (NA), and sweetened alcohol with naringin (SOH + NA) groups. SOH and SOH + NA rats received 10% alcohol + 20% fructose in gelatine; SOH + NA and NA rats received 50 mg/kg naringin in gelatine daily for 10 weeks. Echocardiography was performed to assess left ventricular (LV) function. LV cardiomyocyte diameters and collagen area fraction were determined by H&E and picrosirius-red staining, respectively. In males, sweetened alcohol and naringin did not affect cardiac function. Female SOH rats had increased LV end-diastolic posterior wall (p = 0.04), relative wall thicknesses (p = 0.01), and LV cardiomyocyte diameters (p = 0.005) compared with control. Female SOH and SOH + NA had reduced lateral e' and e'/a' and increased E/e' (p < 0.0001). Female SOH (p = 0.01) and SOH + NA (p = 0.04) rats had increased LV collagen area fraction compared with controls. In males, neither sweetened alcohol nor naringin affected cardiac geometry or diastolic function. In females, sweetened alcohol induced concentric remodelling, impaired LV relaxation, and elevated filling pressures. Naringin may have the potential to improve the sweetened alcohol-induced concentric remodelling; however, it did not ameliorate diastolic dysfunction in females.

After COVID-19 long term respiratory symptoms and reduced lung function including maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) have been reported. However, no studies have looked at MIP and MEP in all disease groups and the reference materials collection methods differ substantially. We aimed to determine MIP and MEP in individuals after COVID-19 infection with different disease severity using reference material of healthy control group obtained using the same standardized method. Patients with COVID-19 were included March 2020-March 2021 at Rigshospitalet, Denmark. MIP and MEP were measured using microRPM. Predicted MIP and MEP were calculated using reference material obtained from 298 healthy adults aged 18-97 years using the same method. In SECURe, 145 participants were measured median 5 months after COVID-19 diagnosis and of these 16% had reduced MIP and/or MEP. There was reduced spirometry and total lung capacity, but not reduced diffusion capacity in those with abnormal MIP and/or MEP compared with normal MIP and MEP. Of those with reduced MIP and/or MEP at 5 months, 80% still had reduced MIP and/or MEP at 12 months follow-up. In conclusion, few have reduced MIP and/or MEP 5 months after COVID-19 and little improvement was seen over time.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45⁺CD11b⁺ day 3 to 14.0 ± 2.6%CD45⁺CD11b⁺ day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.

Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

This study investigated the coactivation of plantar flexor and dorsiflexor muscles and oxygen uptake during running with forefoot and rearfoot strikes at 15 and 19 km/h. We included 16 male runners in this study. The participants ran each foot strike pattern for 5 min at 15 and 19 km/h on a treadmill. During the running, respiratory gas exchange data and surface electromyographic (EMG) activity of the medial gastrocnemius (MG), lateral gastrocnemius (LG), soleus, and tibialis anterior muscles of the right lower limb were continuously recorded. The indices of oxygen uptake, energy expenditure (EE), and muscle activation were calculated during the last 2 min in each condition. During the stance phase of running at 15 and 19 km/h, activation of the tibialis anterior and MG muscles was lower and higher, respectively, with forefoot strike than with rearfoot strike. The foot strike pattern did not influence the oxygen uptake. These results suggest that the foot strike pattern has no clear effect on the oxygen uptake when running at 15 and 19 km/h. However, forefoot strike leads to plantar flexion dominance during co-contraction of the tibialis anterior and MG muscles, which are an antagonist and agonist for plantar flexion, respectively, during the stance phase.

Pulmonary surfactant serves as a barrier to respiratory epithelium but can also regulate airway smooth muscle (ASM) tone. Surfactant (SF) relaxes contracted ASM, similar to β₂-agonists, anticholinergics, nitric oxide, and prostanoids. The exact mechanism of surfactant relaxation and whether surfactant relaxes hyperresponsive ASM remains unknown. Based on previous research, relaxation requires an intact epithelium and prostanoid synthesis. We sought to examine the mechanisms by which surfactant causes ASM relaxation. Organ bath measurements of isometric tension of ASM of guinea pigs in response to exogenous surfactant revealed that surfactant reduces tension of healthy and hyperresponsive tracheal tissue. The relaxant effect of surfactant was reduced if prostanoid synthesis was inhibited and/or if prostaglandin E₂-related EP₂ receptors were antagonized. Atomic force microscopy revealed that human ASM cells stiffen during contraction and soften during relaxation. Surfactant softened ASM cells, similarly to the known bronchodilator prostaglandin E₂ (PGE₂) and the cell softening was abolished when EP₄ receptors for PGE₂ were antagonized. Elevated levels of PGE₂ were found in cultures of normal human bronchial epithelial cells exposed to pulmonary surfactant. We conclude that prostaglandin E₂ and its EP₂ and EP₄ receptors are likely involved in the relaxant effect of pulmonary surfactant in airways.