Physiological Reports最新文献

Ischemic preconditioning (IC) has been studied for its cardiovascular benefits, yet little is known about its effects in older adults with knee osteoarthritis (KOA). The purpose of this study is to explore the impact of a single IC session on markers of cardiovascular health and metabolic efficiency in adults with KOA. Participants were assigned using block randomization to either an IC group or a sham control group. Blood pressure (BP), augmentation index (AIx), pulse wave velocity (PWV), and walking economy (WE) measurements were taken. Both groups were subjected to five cycles of occlusion followed by reperfusion for 5 min each, for a total of 50 min. For the IC group the cuff was inflated to 225 mmHg to fully occlude arterial blood flow while the sham group received cuff inflation at 25 mmHg that did not induce ischemia. BP, AIx, PWV, and WE were measured after the intervention. A small but significant increase in systolic and diastolic blood pressure was observed in the IC group compared to the control group. However, no significant changes were found in PWV, AIx, and WE. These findings suggest that even a single session of IC may influence blood pressure regulation in older adults with KOA, though its effects on vascular function remain unclear. This study provides insight into the effects of IC on blood pressure in older adults with KOA. Further studies are needed to explore the underlying mechanisms and potential therapeutic applications of repeated sessions of IC in older individuals with joint pathology.

Acute renal failure with severe loin pain and patchy renal ischemia after high-intensity exercise (ALPE) is a rare form of acute kidney injury. This study examined the role of vasopressin and its receptor, AVPR1A, in ALPE using a mouse model of brief high-intensity treadmill exercise. Hypoxia-reporter mice received vasopressin after treadmill running (Treadmill + Vasopressin group), whereas controls received vasopressin alone. Renal ischemia and hypoxia were assessed by in vivo imaging system (IVIS) after D-luciferin injection and confirmed by pimonidazole staining. Renal blood flow and vascular resistance were measured in anesthetized mice. The effects of the AVPR1A antagonist SR49059 were also evaluated. The Treadmill + Vasopressin group showed a rapid decrease in renal blood flow and an increase in vascular resistance compared with the Vasopressin group. Pimonidazole staining revealed marked hypoxia at the corticomedullary junction, which was minimal in controls. Bioluminescence indicated renal hypoxia lasting up to 48 h. SR49059 attenuated these changes, supporting an AVPR1A-mediated mechanism. These findings implicate vasopressin in the pathogenesis of ALPE via AVPR1A-dependent vasoconstriction that leads to renal ischemia and support AVPR1A antagonism as a potential therapeutic strategy for ALPE.

Hyperthyroidism generates a hypermetabolic state that promotes adaptations in the skeletal muscle and peripheral nerves leading to deleterious effects. However, there is a paucity of data and conflicting evidence on the influence of thyroid hormones on muscles with predominantly glycolytic fibers and on peripheral nerves. We assessed the contractility, oxidative stress, and muscle fiber composition in the extensor digitorum longus (EDL) and diaphragm, in addition to assessing the nerve conduction in isolated sciatic nerve in a Wistar rat model of chronic hyperthyroidism, induced by levothyroxine over 13 weeks. In hyperthyroid rats, the EDL increased the speed of relaxation associated with loss of muscle mass and reduction in superoxide dismutase (SOD) activity. The diaphragm gained resistance to fatigue associated with an increment in type IIa fibers at the expense of type I and IIb fibers and an increase in SOD and catalase (CAT) activities. In the sciatic nerve, latency, time to peak, and duration of compound action potential were maintained. Chronic hyperthyroidism elicits differential muscle-specific adaptations. While the diaphragm enhances fatigue resistance and antioxidant response, the EDL undergoes atrophy and diminished antioxidant capacity. The observed changes in the sciatic nerve highlight the systemic impact of hyperthyroidism beyond direct muscle effects.

The main transcriptional coactivator of the WNT pathway, β-catenin, is a well-established regulator of adipogenesis and fat expansion, but our knowledge of how other members of the catenin family participate in adipogenesis remains incomplete. Previous studies have elucidated a role for the β-catenin homolog, plakoglobin, in the regulation of adipogenesis in vitro, as its depletion impaired lipid accumulation. Moreover, plakoglobin overexpression in murine cardiomyocytes has been reported to enhance adipogenesis within the heart, further implicating its role as a key regulator of differentiation. In the present study, we investigated the adipocyte-specific contributions of plakoglobin to adipogenesis and metabolism. Although deletion of plakoglobin in mature adipocytes had sex-specific effects on body weight gain, whereby only chow-fed knockout females weighed more than controls, no differences in adiposity or adipocyte size were observed. Moreover, no differences in glucose tolerance or insulin sensitivity were noted. Challenging mice with a high-fat diet revealed diet-induced metabolic disturbances only in male mice, but had no impact on adiposity or body weight. Together, our data demonstrate that plakoglobin in mature adipocytes is not required for adipogenesis or the expansion of adipose tissue mass.

Long-haul travel poses significant challenges to sleep in elite athletes, yet evidence-based interventions tested in competitive settings remain scarce. This study investigated the effects of timing-based interventions on sleep in 10 national-level Canadian speed skaters prior to a World Cup competition in Beijing (13 time zones crossed). Athletes followed a tailored sleep schedule upon arrival and for the days preceding the competition. Total sleep time in Beijing was not different from Canada (p = 0.254) or pre-season (p = 0.999) and was lower the night before travel (p < 0.001) due to the early flight to Beijing. When comparing data with a similar dataset presenting no intervention, bedtime was successfully delayed and resulted in later wake-up time and longer total sleep time. Total sleep time increased by ~10 min/night, suggesting adjustments in sleep-wake rhythm during the first days upon arrival were still present. Race performance was unaffected by travel, with no time effect on overall rank (p = 0.74). These preliminary findings suggest that individualized timing-based strategies might support sleep regulation and circadian re-synchronization in elite athletes following long-haul travel. Further studies are warranted to confirm these results in larger samples and explore the effectiveness of customized timing-based intervention on different time changes and on performance.

Cerebrovascular CYP450 is underexplored in humans. Twenty-three participants (12 females) completed familiarization and two experimental visits utilizing double-blind, randomized, crossover design. Participants ingested fluconazole (150 mg; FLZ, CYP450 inhibitor) or placebo (PLC, microcrystalline cellulose) followed by 120 min of supine rest. Five minutes of middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were collected during rest (PLC/FLZ_BASE) and lower body negative pressure (LBNP; -20 mmHg; PLC/FLZ_LBNP). There was no interaction for MCAv, cerebrovascular conductance index (CVCi), resistance area product (RAP), critical closing pressure (CrCP), or transfer function variables. Bonferroni tests revealed only FLZ attenuated MCAv (FLZ_BASE 75.2 ± 11.3 cm•s^-1 vs. FLZ_LBNP 70.6 ± 11.2 cm•s^-1, p = 0.015, d = 0.713) and CVCi (FLZ_BASE 0.76 ± 0.12 cm•s^-1•mmHg^-1 vs. FLZ_LBNP 0.71 ± 0.11 cm•s^-1•mmHg^-1, p = 0.003, d = 0.865) during LBNP. LBNP lowered CrCP (PLC_BASE 29.7 ± 9.3 mmHg vs. PLC_LBNP 25.1 ± 11.3 mmHg, p = 0.002, d = 0.940) within PLC. RAP increased during LBNP (PLC_BASE 0.96 ± 0.29 vs. PLC_LBNP 1.08 ± 0.32, p = < 0.001, d = 1.28; FLZ_BASE 0.98 ± 0.24 vs. FLZ_LBNP 1.07 ± 0.23, p = < 0.001, d = 1.10). These data suggest a participatory, nonobligatory role of CYP450 in human cerebrovascular control.

This study aimed to evaluate the acute metabolic effects of oral ketone esters (KE) in individuals with and without metabolic syndrome (MetS) on resting energy expenditure (REE), respiratory exchange ratio (RER), and substrate utilization using respiratory gas exchange. Eight participants with MetS and 8 without MetS matched for age, race, and ethnicity completed a randomized, single-blind, placebo-controlled crossover study. Participants underwent a cardiometabolic screening to confirm MetS, followed by two experimental trials. Respiratory gases were measured for 15 min at baseline and 45 and 105 min after a randomly assigned KE or placebo beverage. Following KE ingestion, RER, carbohydrate oxidation (CarbOx), and blood ketones increased significantly, while blood glucose and fat oxidation (FatOx) decreased significantly, irrespective of group. The MetS group showed higher βHB responses to the KE condition than their matched controls, but blood glucose reductions were comparable between groups. Substrate oxidation was similar between the MetS and matched control groups across conditions. Irrespective of MetS status, oral KE acutely increase CarbOx and RER, while concurrently reducing FatOx, without altering REE, suggesting that substrate utilization shifts toward greater CarbOx following KE. Exogenous ketosis may be a promising nonpharmacological strategy to improve metabolic function in individuals with or at risk for MetS.

Pulmonary congestion is a common complication in critically ill patients, but its quantification remains challenging. The wet-to-dry (W/D) lung weight ratio, widely used in experimental models, is a terminal and semi-quantitative method. Lung ultrasonography (LU) may offer a non-invasive and reproducible alternative for assessing pulmonary edema. To evaluate the accuracy and reproducibility of LU compared with the W/D ratio in a rat model of oleic acid-induced lung injury. Thirty Wistar-Kyoto rats were randomized into injury (oleic acid, n = 15) and control (saline, n = 15) groups. Echocardiography and LU were performed at baseline and 1 h after infusion. B-line scoring was independently analyzed by two echocardiographers, with reproducibility assessed by Bland-Altman plots. Evans blue dye evaluated vascular permeability. Oleic acid-treated rats showed significantly higher LU scores, B-line counts, W/D ratios, and Evans blue levels than controls. LU demonstrated good diagnostic performance in detecting lung edema in this experimental model, with excellent inter- and intraobserver agreement confirming strong reproducibility. LU proved accurate, reproducible, and non-terminal for detecting pulmonary congestion in rats, showing good agreement with traditional gravimetric measures and supporting its use for longitudinal assessment of pulmonary edema in experimental research.

This project studied the effects of regional body composition on the core temperature responses to water immersion. Forty-six volunteers participated in the study, with subgroups of eighteen immersed from the neck down in 18, 22, and 26°C water for up to 10 h, respectively. Regional body composition was measured by Dual-energy X-ray Absorptiometry. Rectal temperature (Tc), and 10-site mean skin temperatures (Tsk) were measured every minute. Immersion durations ranged from 0.83 to 10 h, and Tc ranged from 35.2 to 38.0°C at the end of immersion. Tc cooling rates were calculated over the first 0.83 h of immersion. Tc cooling rates varied widely, ranging from -0.37 to 0.93°C/h, -0.39 to 1.87°C/h, and -0.13 to 1.13°C/h at 18, 22 and 26°C water, respectively. The trunk fat mass was negatively and significantly correlated to Tc cooling rates (-0.58, -0.76, 0.60, -0.64, p ≤ 0.01) at 18, 22, 26°C water and across all temperatures combined. The arm fat mass, fat percentage and surface-to-mass ratio were negatively and significantly correlated with Tc cooling rates at most conditions, but not all. Individuals with high cooling rates (≥0.6°C/h) had on average half the trunk fat mass of those with low cooling rates (≤0.25°C/h), and those with low trunk fat mass are least capable of defending core body temperature.