Physiological Reports最新文献

The microcirculation comprises small vessel networks that regulate blood perfusion within tissues. The relationship between tissue shape or size and its microvascular properties is not yet clear. This study develops an algorithm for computationally simulating branching arteriolar networks within ellipsoidal tissue volumes, including user-adjustable parameters (e.g., tissue width-length-height dimensions and microvessel density) for application within different rodent skeletal muscles. The algorithm is developed using principles from constrained constructive optimization, an iterative network generation framework based on proposed mechanisms of vascular growth. Networks generated within muscles of varying shapes and sizes were analyzed over a range of geometric (e.g., mean diameter, length, and number of bifurcations per Strahler's and centrifugal order, fractal dimension) and hemodynamic (e.g., Murray's law exponent, hematocrit) properties. Statistical similarity was observed across different skeletal muscle tissues, with differences due to tissue shape being observed only above a vessel diameter threshold of ~25 μm (varying at large or small tissue volumes at the scale m³ or mm³). The algorithm was comprehensively validated against in vivo data using different modeling approaches (whole tissue vs. subsection simulations). The algorithm's accuracy and adaptability support a wide range of research objectives and contributes to advancing current understanding of perfusion distribution in healthy tissue.

Salt-sensitive hypertension (SS-HT) represents a clinically heterogeneous and mechanistically distinct phenotype of blood pressure dysregulation in which sodium intake disproportionately elevates blood pressure. SS-HT affects up to 50%-60% of individuals with hypertension globally, with an even greater burden among individuals of African ancestry, postmenopausal women, and those with obesity or metabolic syndrome. SS-HT arises from multifactorial dysregulation of renal, vascular, and immune systems. Central to its pathophysiology is aberrant activation of the epithelial sodium channel (ENaC), which drives sodium reabsorption in the distal nephron. ENaC activity is enhanced by both aldosterone-dependent and -independent mechanisms. Concurrently, high dietary sodium induces oxidative stress through NADPH oxidase-mediated reactive oxygen species (ROS) production, disrupts nitric oxide (NO) signaling, and activates antigen-presenting dendritic cells, triggering T-cell-mediated vascular and renal inflammation. This review proposes a systems-level framework in which SS-HT reflects the convergence of ENaC hyperactivation, immunometabolic priming, and hormonal modulation, shaped by sex, race, and dietary sodium-potassium imbalances. Understanding SS-HT as a multifaceted systems disorder opens new avenues for personalized prevention and treatment. Population-specific interventions, such as ENaC-targeting therapies, potassium-enriched diets, and sex and ancestry-informed modulation of the renin-angiotensin-aldosterone system (RAAS), represent promising strategies for precision medicine.

Microvascular control mechanisms involved in the blood flow response to muscle contractions have been well documented in males but remain poorly understood in females. Therefore, we characterized arteriolar vasodilation in situ using intravital microscopy of the retractor muscle of anesthetized female and male hamsters (8-13 weeks). Arterioles were stimulated physiologically by contracting 3-5 skeletal muscle fibers overlying the arteriole for 2 min using a range of twitch and tetanic stimulation parameters: 6, 15, and 60 contractions per minute (cpm) at 20 Hz, or 4, 20, and 70 Hz at 15 cpm (250 ms train duration) and pharmacologically via 2 min micropipette application of nitric oxide (NO, 10^-5 M), adenosine (ADO, 10^-6 M) and potassium (K⁺, 20 mM) as well as acetylcholine (ACh, 10^-6 M) to assess local and conducted responses. Sex differences were not observed in the magnitude or rate of arteriolar vasodilation under any physiological or pharmacological condition. Collectively, these data demonstrate that arteriolar reactivity to muscle contractions and to pharmacological stimuli relevant to muscle contractions, were not different between females and males. These data suggest that the integrated vascular response during active hyperemia may not be sexually dimorphic.

This study examined the effects of different types of acute exercise on salivary expression levels of human herpesvirus 6 (HHV-6) and 7 (HHV-7). In a randomized crossover trial, 11 healthy untrained men performed a continuous exercise (CE) trial (20 min at 70% $\dot{V}O$ ₂max) and an interval exercise (IE) trial (20-min cycling: five sets of 2-min at 50% $\dot{V}O$ ₂max and 2-min at 90% $\dot{V}O$ ₂max). Salivary HHV-6 and HHV-7 DNA expression was measured using real-time PCR, and maximum voluntary contraction (MVC) of knee extensors was assessed after saliva collection. Salivary HHV-6 expression increased at post-0 min (p < 0.001) and post-30 min (p = 0.002) in IE compared with pre, and was higher in IE than CE at both time points (p = 0.002, p = 0.048 respectively), but salivary HHV-7 expression did not change between trials. Changes in serum IL-6 and blood lactate levels were significantly higher in IE than in CE at post (p < 0.001). The sum of time-dependent changes in MVC was significantly lower in IE than CE (p = 0.016). Change in salivary HHV-6 from pre to post-24 h was negatively correlated with change in MVC (r_s = -0.349, p = 0.047). These results suggest that IE may increase salivary HHV-6 expression and that changes in salivary HHV-6 may reflect objective physical fatigue after acute IE.

The E-cigarette or Vaping product-Associated Lung Injury (EVALI) causes severe acute respiratory failure and, in some cases, death. Most cases are linked to tetrahydrocannabinol-containing e-cigarette products adulterated with vitamin E acetate. Despite regulation and awareness efforts, VEA persists in biological samples from EVALI patients and remains a public health concern, particularly among adolescent males. The mechanisms driving VEA-induced lung injury, and how they may be differentiated by sex, remain poorly understood. To address this, age- and size-matched adolescent male and female mice were exposed to aerosolized VEA for 3 or 10 days. By Day 10, VEA exposure caused histopathologic lung injury and systemic inflammation, with alveolar barrier dysfunction evident on Day 3. Male mice developed more severe injury and immune dysregulation, with elevated lung interleukin-1β, interleukin-6, and keratinocyte chemoattractant and reduced expression of club cell secretory protein along the airway epithelium. Female mice showed higher serum levels of soluble receptor for advanced glycation end products, a biomarker of alveolar injury and inflammation that also functions as an immune modulator. This is the first study to identify sex-specific differences in pulmonary responses to VEA exposure. These findings offer insight into EVALI immunopathogenesis and may explain population-level sex disparities in disease severity.

Sensory processing disorder (SPD) is a neurodevelopmental condition characterized by impaired sensory discrimination and responsivity. Although the causes and neural correlates of SPD remain poorly understood, prenatal influences should be considered, as the prenatal environment is strongly implicated in the progression of neurodevelopmental disorders. One factor hypothesized to promote SPD is perinatal Western-style diet (WSD) exposure. This study explored the effects of perinatal WSD exposure on the proposed neural correlates of SPD in Japanese macaques. Functional connectivity between sensory and emotional processing areas was assessed at 4 months of age using resting-state functional magnetic resonance imaging (rs-fMRI). A machine learning model successfully predicted perinatal diet group based on functional connectivity strengths, indicating that differences in sensory connectivity exist between diet groups. Intra-somatomotor, visual-auditory, somatomotor-auditory, somatomotor-visual, and intra-visual network connections demonstrated the greatest differences between groups, with primary motor cortex connectivity being the most impacted. Connections to the amygdala were not major contributors to accurate model performance, but amygdala connectivity, especially to the somatomotor network, may still be a weak driver of model performance. These findings suggest that a proposed predictor of SPD, perinatal WSD exposure, impacts the functional connectivity of sensory processing areas relevant in SPD during early infancy.

Early-life inflammation has a long-lasting impact on pain behaviors, with neonatal inflammation resulting in altered pain behaviors throughout life. Possible mechanisms underlying these changes lie within the first and second order neurons in the pain neuroaxis. We investigated neuroinflammatory markers in dorsal root ganglia (DRGs) and spinal cords (SC) of Wistar rats (both sexes) following neonatal injection with either LPS or saline (postnatal days (P) 3 and 5) and isolated tissues in early postnatal development. RT-qPCR revealed acute neuroinflammation in the DRGs, with expression levels of four inflammatory mediators elevated at P7, two at P13, and none at P21 in LPS-treated rats. In contrast, the SC showed no change in inflammatory mediators at P7, elevation of two at P13 and four at P21 in LPS-treated rats. These differences were greater in female SCs, indicating sex-specific modulation even at these early stages of postnatal development. The SCs of P21 LPS-treated rats also showed sex-specific modulation of astrocytes (GFAP), with females showing an increase and males a decrease in GFAP. Together, these data indicate that during early postnatal development DRG neurons are more susceptible to acute inflammation whereas inflammation is delayed in the SC, with sex-specific modulation occurring only in the SC.

The optimization of cerebral perfusion and sedation using autoregulation-derived physiologic targets such as optimal cerebral perfusion pressure (CPPopt), optimal mean arterial pressure (MAPopt), and optimal bispectral index (BISopt) has emerged as a promising strategy in neurocritical and perioperative care. However, the reliability and comparability of these optimal (Opt) parameters across different autoregulatory indices remain uncertain. This paper systematically reviews and synthesizes literature comparing CPPopt, MAPopt, and BISopt derived from invasive and noninvasive indices. Following PRISMA-ScR guidelines, studies directly comparing CPPopt, MAPopt, or BISopt from at least two indices were included. Ten studies compared CPPopt, mostly in traumatic brain injury, with mean values between 70 and 76 mmHg. Nine studies compared MAPopt, reporting strong correlations between transcranial doppler-, near-infrared spectroscopy-, and intracranial pressure-derived indices across populations, though limits of agreement were wide. One study compared BISopt across indices, showing internal consistency, while two cross-Opt studies found little correlation between BISopt and CPPopt or MAPopt. CPPopt and MAPopt appear physiologically robust across indices, supporting translational potential in both invasive and noninvasive settings. BISopt may represent a distinct optimization domain related to sedation rather than perfusion. Methodological heterogeneity and limited outcome validation remain barriers. Future work should emphasize standardization, multimodal integration, and outcome-driven trials.

Perivascular adipose tissue (PVAT) regulates vascular tone, and high-fat diets reportedly lead to the loss of its anti-contractile properties. Methionine restriction recapitulates many caloric restriction metabolic effects and increases liver expression of activating transcription factor 4 (ATF4) and downstream targets with anti-contractile properties such as cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). We hypothesized that dietary methionine restriction would prevent high-fat diet-induced PVAT dysfunction by increasing ATF4 expression. Male Wistar rats were fed control (C, 10% calories from fat) or high-fat diets (H, 60% calories from fat) (HFD) that were methionine replete (R, 0.86% methionine) or deplete (D, 0.12% methionine) for 12 weeks. Methionine restriction prevented body mass increases, independent of fat content, and had no effect on blood pressure or arterial contraction to norepinephrine (10 μM) or relaxation to acetylcholine (10 μM). In this feeding paradigm, HFD did not induce PVAT dysfunction. CR diet increased ATF4 transcript levels in multiple PVAT depots but did not consistently affect expression of downstream targets. Protein expression of ATF4 and its targets varied largely for all groups. In conclusion, 12 week methionine restriction profoundly affected body mass but not blood pressure or arterial reactivity in the presence or absence of PVAT.