Physiological Reports最新文献

Determine how matched duration but varied exposure scheduling impacts heat acclimation in male and female adults. Thirty males and thirty females walked daily (7 days, 38°C, 60% RH, 6.1 METs) in one of four groups (sustained males/females [SM/SF], periodic males/females [PM/PF]). SM/SF performed 90-min exposures; PM/PF completed three 30-min exposures 3 h apart. Females had similar ovarian-hormone fluctuation. Acclimation markers were assessed within the first 30-min exposure on days 1, 4, and 7. SM/SF rectal temperature decreased from day 1 to days 4 and 7 (37.5 ± 0.3°C, 37.3 ± 0.3°C, 37.2 ± 0.3°C, p < 0.001) and further decreased from day 4 to 7 (p = 0.011). PM/PF rectal temperature was unchanged between days 1, 4, and 7 (37.4 ± 0.3°C, 37.4 ± 0.3°C, 37.3 ± 0.3°C, p > 0.05). SM/SF 3-site surface temperature decreased from day 1 to days 4 and 7 (37.1 ± 0.5°C, 36.9 ± 0.4°C, 36.8 ± 0.4°C, p < 0.001) but was unchanged from day 4 to 7 (p = 0.090). PM/PF 3-site surface temperature was unchanged from day 1 (37.0 ± 0.4°C) to days 4 (37.0 ± 0.4°C, p = 0.726) and 7 (36.9 ± 0.4°C, p = 0.109) but decreased from day 4 to 7 (p = 0.013). Females had higher rectal (p < 0.001) and 3-site surface (p = 0.036) temperatures than males throughout acclimation. Thrice-daily exposures are not as effective at inducing heat adaptations compared to once-daily exposures. Sex differences persisted throughout acclimation without altering adaptations.

This study investigated the associations between body composition and autonomic cardiac regulation, indexed by heart rate variability (HRV), in clinically healthy young adults, and additionally explored complementary breathing rate variability (BRV) and pulse-respiratory quotient (PRQ) indices. Ninety university students aged 18-23 years (35 men, 55 women) were evaluated. Linear and nonlinear HRV and BRV indices were derived from 5-min R-R and breath-to-breath and PRQ time series. Body mass index (BMI) and bioelectrical impedance-based measures were obtained, including fat mass percentage (%FM), muscle mass, and visceral fat indices. HRV, BRV, PRQ, and composition indices were analyzed, and sex-stratified correlations between body composition and autonomic indices were examined. Men showed greater respiratory variability and lower breathing rate than women. In men, BMI, %FM, and visceral fat indices correlated negatively with parasympathetic modulation and the complexity of cardiac and PRQ series, and positively with sympathetic modulation. In multivariable regression models adjusted for age, breathing rate, and physical activity (assessed with the IPAQ-short form and expressed as total METs/week), higher %FM was independently associated with lower vagally mediated HRV indices in men, but not in women. Higher adiposity (higher BMI, %FM, and visceral fat indices), particularly in young men, was associated with reduced vagal HRV and diminished cardiorespiratory complexity.

Perceptual decision-making processes, particularly in the context of eye movements and reaction times (RT), have been studied to better understand how the brain integrates and responds to sensory information. Recent models have decomposed the process into multiple intermediate steps, including detection, instruction processing, decision, and motor response. To investigate the impact of the observer's expectations on each of these steps, we conducted two experiments on 24 participants (including both female and male participants), manipulating respectively the stimuli's location expectation (left or right) and the eye movement expectation (saccade or antisaccade). The results revealed limited evidence for the influence of location expectation on saccadic RT and moderate evidence for antisaccadic RT. Conversely, there was strong evidence of the influence of movement expectations on both movements' RT. This suggests an asymmetric impact of expectations on the different steps of perceptual decision-making, with strong impact on motor response and instruction processing. These findings challenge the common attribution of expectation effects solely to the decision-making module from previous works, emphasizing the importance of considering multi-module integration in perceptual decision models.

Red blood cells from individuals with type 2 diabetes (T2D RBC) induce endothelial dysfunction due to reduced RBC microRNA-210 levels, whereas T1D RBCs do not. We hypothesize that microR-210 plays a protective role explaining this difference. Both male and female adults with T1D and T2D matched for glycated hemoglobin, alongside age- and sex-matched healthy controls, were studied. microR-210 levels were measured by qPCR. Endothelium-dependent relaxation (EDR) in isolated rat aortas and nitric oxide (NO) production in endothelial cells following incubation with RBCs were determined using wire myograph and DAF-FM fluorescence. Protein levels of microR-210 target PTP1B and the oxidative stress marker 4-HNE were measured by immunohistochemistry. T1D RBC produced EDR and endothelial NO comparable to healthy controls, whereas T2D RBC impaired both. microR-210 levels were similar in T1D RBC and healthy controls, but reduced in T2D RBC. microR-210 inhibition in T1D RBC impaired EDR and increased vascular PTP1B and 4-HNE, while PTP1B inhibition or mitoTEMPO treatment in aortas improved EDR. RBC microR-210 regulates endothelial function differently between T1D and T2D by affecting vascular PTP1B and mitochondrial oxidative stress, highlighting a potential therapeutic target to improve vascular health.

This study examined how sex influences blood flow during exercise at altitude and relative contributions of adrenergic mechanisms. Thirteen participants (8 M/5F) were tested at low and high altitude (days 3-11). Participants performed rhythmic handgrip for 3 min at 25% maximal voluntary contraction during local infusions of saline, propranolol (β-adrenergic blockade), and phentolamine with propranolol (α-β-adrenergic blockade). Doppler ultrasound was used to examine brachial artery blood flow (FBF) and calculate forearm vascular conductance (FVC). Resting FBF and FVC were higher in males compared to females across all conditions (p = 0.024; p = 0.025, respectively). Blockade condition significantly altered FBF and FVC (p < 0.001 for both) but there was no effect of altitude (p = 0.330; p = 0.718, respectively). During exercise, ΔFBF was influenced by condition (p < 0.001), but not by sex (p = 0.696) or altitude (p = 0.813). Similarly, ΔFVC was different across conditions (control: 9.4 ± 2.3 mL/min/mmHg/FAV; β-blockade: 11.4 ± 12.8 mL/min/mmHg/FAV; α-β-blockade: 3.9 ± 1.1 mL/min/mmHg/FAV; p < 0.001), with no effect of sex (p = 0.646) or altitude (p = 0.889). These results suggest males and females do not respond differently to exercise at altitude, and light-intensity exercise hyperemia may be preserved during early acclimatization. α-adrenergic receptors appear important for exercising blood flow, but β-adrenergic receptors may not be critical in this response.

The lipid mediator 20-HETE is produced by ω-hydroxylation of arachidonic acid mediated by cytochrome P450 (CYP) enzymes including CYP4A, which has four distinct isoforms in rodents. Several laboratories demonstrated that 20-HETE synthesis inhibition reduces infarct volume following middle cerebral artery occlusion (MCAO) in male animals. Here, we investigated whether neuroprotection with the 20-HETE synthesis inhibitor HET0016 administered after transient MCAO in rats differs by sex and whether ischemia differentially induces Cyp4a genes in a sex-dependent manner. HET0016 significantly improved sensorimotor performance and reduced infarct volume compared to vehicle treatment in males. However, these improvements were less consistent in females. Cyp4a2 and Cyp4a3 genes were detected at similar levels in brain tissue from male and female rats undergoing sham surgery or MCAO/reperfusion. Interestingly, the Cyp4a8 gene was detectable in intact and castrated males and increased 3-4-fold after MCAO. In contrast, Cyp4a8 was undetectable in brains of intact or ovariectomized female rats. Oxygen-glucose deprivation in cultured murine neurons revealed male-selective induction of the homolog gene Cyp4a12a, the knockdown of which blocked the increase in 20-HETE. These results indicate that innate male-selective Cyp4a gene induction and 20-HETE signaling are significant factors that can contribute to sex differences in the outcomes from ischemic stroke.

The airway epithelium serves as the first line of defense against inhaled insults present in the external environment by acting as a physical barrier and through host defense mechanisms. Proper maintenance of these host defense mechanisms relies on the regulation of airway surface liquid (ASL) composition and properties, a process that is tightly controlled by various ion transporters, including the cystic fibrosis transmembrane conductance regulator (CFTR) protein. With evidence suggesting dysfunctional CFTR-mediated bicarbonate secretion leads to airway acidification, resulting in impaired host defenses, there is increased interest in improving ASL pH. The aim of our study was to determine whether pharmacological interventions, via cAMP and CFTR modulators, lead to an increase in pH. Human airway epithelial (Calu-3) cells were exposed to various combinations of cAMP and CFTR modulating agents to assess their effectiveness at elevating apical base secretions (apical fluid) pH. Our results show that pharmacological interventions with cAMP elevating agents and CFTR modulator VX-770 led to significant increases in pH, with combinations leading to greater increases compared to single drug interventions. Our study suggests that cAMP and CFTR modulation has potential as a therapeutic strategy for elevating ASL pH and may be beneficial for respiratory diseases with ASL abnormalities.

Seasonal differences in temperature and ultraviolet radiation (UVR) exposure may alter NO-mediated vasodilation in the cutaneous microvasculature. We assessed seasonal variation in cutaneous microvascular function in 10 healthy (23 ± 2; 6 men, 4 women) adults in the summer/early-fall and winter/early-spring. Microvascular (intradermal microdialysis and local skin heating [42°C]) endothelial function was assessed at two visits separated by ~6 months. Mean daytime (sunrise to sunset) outdoor temperature and 2-h peak UV Index were recorded for the 30 days prior to each experimental visit. Serum vitamin D concentrations [25(OH)D] were measured for each visit. Multivariate regression analysis evaluated the factors (temperature, UV Index, and [25(OH)D]) that best explained variance in microvascular endothelial function. The local heating response (74.37 ± 12.21 %CVC_max vs. 55.89 ± 15.50 %CVC_max, p = 0.009) and the NO contribution to that response (61.73% ± 9.67% vs. 38.13% ± 13.26%, p = 0.004) were lower in winter/early-spring compared to summer/early-fall. The best-fit regression model suggested that 30-day average outdoor temperature and 2-h peak UV Index were positively and negatively associated with NO-dependent cutaneous vasodilation, respectively. Healthy adults exhibit lower NO-mediated cutaneous vasodilation in the winter/early-spring compared with summer/early-fall, which is partially explained by seasonal differences in outdoor temperature.

Microgravity exposure during spaceflight induces a thoracocephalic fluid shift that affects the cardiovascular system both during flight and after return to Earth. As the proportion of female astronauts increases, it is essential to understand how altered gravity impacts cardiovascular function across sexes. In this study, we examined sex differences in central hemodynamics, vascular morphology of the common carotid artery and internal jugular vein (IJV), and IJV pressure during graded head-up to head-down tilt (+45° to -45° in 15° increments) in healthy participants (12 female and 12 male adults). A strong gravitational dependence on almost all variables was observed, except for oxygen consumption. Only a few variables showed significant sex differences, and these include cardiac output, total peripheral resistance, rate pressure product, oxygen consumption, and sympathovagal balance (LF/HF ratio). Overall, hemodynamic, vascular morphology, and IJV pressure responses to tilt were largely similar between sexes. The additional female gravitational dose-response curves augment our previous, male-only database of cardiovascular responses to tilt. Together, these results provide a unique and more comprehensive normative baseline to support the development of spaceflight countermeasures as well as other terrestrial clinical applications, such as surgery in Trendelenburg or prone positioning.

Heart rate variability (HRV) is a sensitive marker of autonomic regulation. This study examined adolescents in the long-term postoperative period after early surgical correction of aortic coarctation (CoA) compared with age-matched healthy peers. Seventy adolescents (35 CoA, 35 controls; 12-17 years) underwent 5-min resting ECG and respiratory monitoring. HRV was analyzed using time domain, frequency domain, and nonlinear methods; respiratory rate was included as a covariate in ANCOVA models. Adolescents with repaired CoA showed lower time domain indices (SDNN, RMSSD, pNN50; all p < 0.01), reduced total spectral power (p = 0.002), and higher VLF (p < 0.001). Group differences in SDNN, RMSSD, and the LF/HF remained significant after adjustment for respiratory rate, indicating that autonomic alterations were not explained by breathing patterns. Nonlinear analysis revealed reduced Poincaré plot parameters (SD1, SD2; p < 0.01) and higher fractal scaling (DFA Alpha2; p < 0.001) in the CoA group, whereas entropy measures and DFA Alpha1 did not differ. These findings demonstrate persistent and selective alterations in autonomic regulation during adolescence despite anatomically successful repair. The coexistence of altered and preserved HRV features suggests domain specific reorganization rather than uniform loss of complexity. Nonlinear HRV indices may improve long term monitoring and help guide individualized rehabilitation.