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

{"title":"Cerebral pressure-flow relationship directional sensitivity in healthy lowlanders and natives at high altitude.","authors":"Shahrzad Soleimani Dehnavi, Jonathan D Smirl, Marc-Antoine Roy, Lawrence Labrecque, François Billaut, Kurt J Smith, Samuel J E Lucas, Philip N Ainslie, Patrice Brassard","doi":"10.1152/ajpregu.00151.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00151.2025","url":null,"abstract":"<p><p>Whether cerebral pressure-flow relationship directional sensitivity, which represents the attenuated changes in cerebral blood velocity in response to transient increases, compared with decreases, in mean arterial pressure (MAP), is altered in lowlanders at high altitude or differs between lowlanders and Sherpa (a well-adapted highlander population of the Nepalese Khumbu region) is unknown. Both MAP and middle cerebral artery mean blood velocity (MCAv) were recorded continuously during 5-min repeated squat-stands (RSS) at 0.05 Hz and 0.10 Hz at sea level (n=10), initial exposure to high-altitude (n=8), after 2 weeks of partial acclimatization to high-altitude (n=9), and in Sherpa (n=16). For each transition, we calculated absolute and relative MCAv and MAP changes with respect to the transition time intervals of both variables indexing time adjusted ratios when MAP increases (ΔMCAv_T/ΔMAP_T^INCREASE and %MCAv_T/%MAP_T^INCREASE) and decreases (ΔMCAv_T/ΔMAP_T^DECREASE and %MCAv_T/%MAP_T^DECREASE). Regardless of altitude conditions, %MCAv_T/%MAP_T^INCREASE was lower than %MCAv_T/%MAP_T^DECREASE [0.05 Hz RSS: (p=0.0.007); 0.10 Hz RSS (p=0.003)] in lowlanders. Partially acclimatized lowlanders and Sherpa had lower %MCAv_T/%MAP_T^INCREASE than %MCAv_T/%MAP_T^DECREASE at 0.05Hz (p=0.007), but comparable metrics at 0.10Hz RSS (p=0.971). These findings indicate acute exposure and partial acclimatization to high altitude do not alter the cerebral pressure-flow relationship directional sensitivity compared to sea level measures in lowlanders . In addition, the hysteresis-like pattern in Sherpa is not different when compared with partially acclimatized lowlanders.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal changes in cardiovascular and sympathetic neural responses to static handgrip exercise throughout pregnancy.","authors":"Takuro Washio, Sarah L Hissen, John D Akins, Ryosuke Takeda, Safia Khan, Andrew R Tomlinson, David B Nelson, Tony G Babb, Qi Fu","doi":"10.1152/ajpregu.00074.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00074.2025","url":null,"abstract":"<p><p><b>Backgrounds:</b> The time-course changes in the exercise pressor response throughout gestation remain unknown. As pregnancy is associated with altered hemodynamics and sympathetic activation, we hypothesized that neural responses to static handgrip (SHG) exercise would be augmented, especially during late pregnancy. <b>Methods:</b> Forty-six women (30±6 yrs [SD]) were studied longitudinally during early and late pregnancy, and postpartum. Mean arterial pressure (MAP), cardiac output (Qc), total peripheral resistance (TPR=MAP/Qc) and muscle sympathetic nerve activity (MSNA) were measured during supine rest and SHG at 40% of maximal voluntary contraction force until fatigue, followed by 2-min post-exercise circulatory occlusion (PECO) to isolate muscle metaboreflex activation. <b>Results:</b> The peak increase (Δ) in MAP during fatiguing SHG did not differ among gestation stages (P=0.669), but ΔMAP during PECO trended smaller in late pregnancy than postpartum (P=0.054). ΔQc during SHG and PECO was larger in late pregnancy compared to early pregnancy and postpartum (P<0.05), while ΔTPR was lower in late pregnancy (P<0.05). ΔMSNA during SHG was not different (P=0.740) but smaller during PECO in late pregnancy compared to early pregnancy and postpartum (P<0.05). Confounding factors like obesity or pregnancy complications did not affect these responses (P>0.05). <b>Conclusion:</b> Sympathetic activation elicited by the muscle metaboreflex was reduced in late pregnancy, which may be related to the blunted peripheral vasoconstriction. Conversely, the cardiac output response to exercise was augmented in late pregnancy. These results suggest that central and peripheral responses are impacted differently to maintain an adequate pressor response to exercise throughout pregnancy, regardless of obesity and complications.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of dynamic cerebral autoregulation efficiency on its directional sensitivity.","authors":"Ronney B Panerai, Aaron Davies, Victoria J Haunton, Abdulaziz Alshehri, Emmanouil Katsogridakis, Lucy C Beishon, Thompson G Robinson, Jatinder S Minhas","doi":"10.1152/ajpregu.00140.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00140.2025","url":null,"abstract":"<p><p>Dynamic cerebral autoregulation (dCA) demonstrates directional sensitivity (DS_CA), depending on increases or reductions in mean arterial blood pressure (MAP). DS_CA dependence on the efficiency of dCA has not been reported. A retrospective study of 172 healthy subjects (88 female, age 19-82 years), with five-minute recordings of MAP, cerebral blood velocity (middle cerebral artery, MCAv), end-tidal CO₂, and electrocardiogram, led to estimates of the MCAv step response to changes in MAP. The strength of DS_CA was expressed by the difference between the MCAv step responses for the positive derivative component of MAP and the corresponding negative derivative component. The efficiency of dCA was expressed by the original autoregulation index (ARI_orig), ranging from 0 to 9, calculated from the original MAP. For the entire population, DS_CA strength was not associated with ARI_orig, or any other parameters. However, when taking biological sex and age into account, markers of DS_CA strength showed significant linear regressions with ARI_orig, with negative slopes for younger females (p=0.0037 to 0.011, late phase of the step responses), no influence in older females (p> 0.69), and positive slopes for both younger and older males (early phase of the step responses, p=0.003 to 0.041). This contrasting pattern of the influences of sex and age is in agreement with the known effects of gonadal hormones on the myogenic response and endothelial function of the cerebral circulation. Clinical studies of the diagnostic and/or prognostic value of DS_CA parameters need to take into account the influences of sex, age and the ARI_orig.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water deprivation test in children: challenging but still necessary for the differential diagnosis of polyuria-polydipsia syndrome.","authors":"Carolina Donaire Sousa, Beatriz Gon Perez Nardoque, Davi Casale Aragon, Ayrton Custódio Moreira, Mariana Teresa Alves Sarti de Paula, Paula Condé Lamparelli Elias, Sonir Roberto Rauber Antonini","doi":"10.1152/ajpregu.00248.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00248.2024","url":null,"abstract":"<p><p>The differential diagnosis within polyuria-polydipsia syndrome, especially in the pediatric population, remains challenging. Despite its limited accuracy, the water deprivation test (WDT) is the reference test in pediatrics. We retrospectively analyzed performed in 65 pediatric patients (mean age 8.2 years; 0-17.9). We evaluated the accuracy and safety of the WDT, investigated possible baseline variables that could predict outcomes, and reevaluated interruption and interpretation criteria. Among the 83 WTDs performed, 47 (56.6%) were conclusive (accuracy= 53%). The simplified 2 hours-WDT was inconclusive in 47.6% of the sample. A baseline urinary osmolality (uOsm) greater than 279 mOsm/kg excluded arginine vasopressin deficiency (AVP-D) and/or AVP resistance (AVP-R) in all patients (sensitivity= 100%; specificity= 74%; p < 0.01). A uOsm greater than 533 mOsm/kg at the time of WTD discontinuation also excluded the diagnosis of AVP disorders in all subjects (sensitivity= 100%; specificity= 100%; p< 0.01). Therefore, a baseline uOsm> 279 mOsm/kg and a peak uOsm> 533 mOsm/kg excluded AVP disorders. These new cut-offs can improve WDT accuracy and should be validated in prospective studies. No serious adverse effects (SAE) were observed. The lower limit of 3% weight loss was the criterion for early WDT interruption in nine conclusive tests. The demonstrated safety encourages us to use weight losses greater than 5% as stopping intervals and also tolerate a more extended test duration when necessary. In conclusion, WDT in children and adolescents is safe and still necessary until better diagnostic tools are proven helpful in pediatric patients with polyuria-polydipsia syndrome.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of sex and heating rate on skin blood flow oscillations during local heating in young adults.","authors":"Gregory W McGarr, Caroline Li-Maloney, Ashley P Akerman, Naoto Fujii, Tatsuro Amano, Glen P Kenny","doi":"10.1152/ajpregu.00167.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00167.2025","url":null,"abstract":"<p><p><b>Objective:</b> to explore sex and heating rate effects on frequency-domain indicators of the mechanisms modulating cutaneous vasodilation during local heating. <b>Materials and Methods:</b> In thirty young adults (21±3 years, 15 females), wavelet analysis of skin blood flux was assessed from laser-Doppler flux signals at the chest, abdomen, arm, forearm, thigh, and calf during rapid (33-42°C; 1°C·20 s^-1) and gradual (33-42°C; 1°C·5 min^-1) local skin heating. A wavelet transform using a Morlet mother wavelet was computed over the entire signal for each heating protocol (minimum 90 minutes) and 5-min time windows were subsequently isolated to determine responses during baseline and the 42°C heating plateau. Wavelet data were decomposed into metabolic, neurogenic, myogenic, respiratory, and cardiac frequency bands and presented as absolute and relative (normalized) amplitudes. <b>Results:</b> There was a significant sex by heating rate interaction for relative wavelet amplitude in the metabolic frequency band (P=0.003), which was 0.89-fold [0.82,0.98] lower (P=0.006) during rapid heating compared to gradual for females only. There were no significant interactions for the other frequency bands (all P≥0.054). Males showed greater absolute and relative amplitudes for neurogenic and myogenic bands compared to females (all P≤0.022). Rapid heating resulted in significantly lower absolute amplitudes for metabolic, neurogenic and cardiac bands compared to gradual heating (all P≤0.004). However, there was a significantly greater relative amplitude for the respiratory band during rapid heating compared to gradual (P=0.030). <b>Conclusions:</b> These exploratory findings highlight important sex and heating rate effects on wavelet-based indicators of the mechanisms modulating cutaneous vasodilation during local heating.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-induced impairments in fasting glucose are associated with acute mountain sickness severity during four days of residence at 4,300 m.","authors":"Sean P Langan, Emily C Tagesen, Steven D Landspurg, Peter S Figueiredo, Quint N Berkemeier, Melissa D McInnis, Robert L Alunday, Aaron J Reilly, Trevor J Mayschak, Erik R Swenson, Pierre A Fabries, Jon K Femling, Beth A Beidleman","doi":"10.1152/ajpregu.00130.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00130.2025","url":null,"abstract":"<p><p>Insulin resistance has been associated with acute mountain sickness (AMS) risk, but the influence of active ascent is unclear.</p><p><strong>Methods: </strong>Thirty-two unacclimatized Soldiers (23±4yr; 80±14 kg) were tested at baseline residence (BLR), hiked ~5 km (n=16) or were driven (n=16) to 4,300 m, and stayed for 4 days (~66 h). Venous blood was taken each morning at BLR and during high altitude (HA) exposure days 2-4 (HA2-4) and the evening on day 1 at HA (HA1). Metabolites and hormones were measured, and insulin resistance (HOMA-IR) was calculated. AMS cerebral factor score (AMS-C) was measured daily and peak scores were calculated.</p><p><strong>Results: </strong>Active ascenders had higher energy expenditure (1,265±351 vs. 408±208 kcal) and lower oxygen saturation (SpO₂) (75±3 vs. 82±3%) during ascent. Norepinephrine and lactate were higher (<i>P</i><0.007) in active ascenders on HA1. All other data were combined due to lack of group differences. Glucose, insulin, and HOMA-IR were elevated (<i>P</i><0.05) on HA2 (105.9 ± 12.3 mg/dl; 12.1 ± 6.8 μIU/ml; 3.2 ± 2.1 au) and HA3 (101.8 ± 11.2 mg/dl; 10.2 ± 5.5 μIU/ml; 2.2±1.4 au) versus baseline and returned to normal on HA4. Epinephrine (<i>P</i><0.001) and cortisol (<i>P</i>=0.004) were elevated on HA1 and HA2 versus baseline, respectively. GLP-1 was higher on HA1 versus HA2 and HA3 (<i>P</i><0.021). Glucose (r_rm=0.42; <i>P</i>=0.001), insulin (r_rm=0.29; <i>P</i>=0.001), HOMA-IR (r_rm=0.27; <i>P</i>=0.002), epinephrine (r_rm=0.34; <i>P</i><0.001), and norepinephrine (r_rm=0.20; <i>P</i>=0.027) were significantly correlated with AMS-C.</p><p><strong>Conclusions: </strong>Transient perturbations to glucose metabolism during 4 days of HA exposure influences AMS severity without further impact from active ascent.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Praeruptorin A alleviates DSS-induced acute ulcerative colitis in mice via the STAT-1/-3 pathway.","authors":"Junshen Xiao, Shichao Wei, Yue Wang, Xuan Zhang, Hangxue Cao, Zhaoyang Hu","doi":"10.1152/ajpregu.00064.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00064.2025","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a serious inflammatory bowel disease with a significantly increasing incidence globally. Current treatment options often exhibit unstable efficacy and notable side effects, making the exploration of alternative therapies particularly important. Peucedanum praeruptorum Dunn, a traditional Chinese medicine, contains various bioactive compounds, among which praeruptorin A (PA) has garnered attention for its anti-inflammatory potential. This study aimed to investigate the anti-UC effects of PA in a dextran sulfate sodium (DSS)-induced colitis mouse model and in Caco-2 cells and its underlying mechanisms. Preliminary results indicate that PA alleviates symptoms of DSS-induced ulcerative colitis, significantly reduces the expression of inflammatory factors, decreases colonic apoptosis, and repairs damaged intestinal barrier function in mice. PA also had protective effects on DSS-induced barrier dysfunction and inflammation in Caco-2 cells. Further research demonstrated that PA inhibits the phosphorylation of the STAT-1 and STAT-3 proteins, whereas AG490, an inhibitor of STAT-1 and STAT-3, effectively mimics the intestinal protective effects of PA. In addition, network pharmacology and molecular docking analyses were conducted to further elucidate the molecular targets and mechanisms of PA. These analyses revealed key pathways and potential interactions, supporting the hypothesis that PA exerts its protective effects through the modulation of inflammatory and apoptotic pathways. In summary, these findings support the protective role of PA in ulcerative colitis in vivo and in vitro and suggest its potential as an intervention for the prevention and treatment of this condition.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145028797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience-mediated transcriptional memory correlates with hypoxia resistance in the nervous system of the sea hare <i>Aplysia californica</i>.","authors":"Javier Antonio Rodriguez Casariego, Phillip Gillette, Michael C Schmale, Mark W Miller, Lynne A Fieber","doi":"10.1152/ajpregu.00071.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00071.2025","url":null,"abstract":"<p><p>Current therapeutics for hypoxic/ischemic brain damage can benefit from insights resulting from the study of hypoxia/anoxia resistant organisms. Hypoxia resistance, however, is not a common feature in mammalian models. Being naturally exposed to hypoxic/anoxic conditions, the sea hare <i>Aplysia californica</i> could become a very useful model for the study of hypoxia resistance. Here we experimentally exposed two cohorts of <i>A. californica</i>, resulting from crosses of adults with different environmental exposure histories, to daily 6h pulses of hypoxic water conditions (<1.8 mgO₂/ml) for 6 consecutive days. The transcriptional response to hypoxia was evaluated in the abdominal and pleural/pedal ganglia through the exposure, during rapid reoxygenation, and after 12+ hours of recovery. Resistance to hypoxia was observed in the offspring of wild animals, with no significant changes in growth and reflex performance, compared to unexposed controls of the same cohort. Impairments were observed however in the offspring of lab-reared individuals. Transcriptional response to hypoxia was larger in the abdominal ganglia compared to the pleural/pedal for both cohorts, and significant differences between cohorts were observed for both ganglia. Overall, wild-cross animals displayed a significant reduction in the expression of metabolic genes, and an increased expression of genes involved in stress-response and immune system functions compared to the lab-cross cohort, both under control conditions and during hypoxia exposures. The resistant group displayed similar gene-level regulation as that described to be involved in hypoxia/ischemia preconditioning (HPC/IPC) in mammalian models, including the frontloading of HIF1-a orthologs and other neuroprotective genes like VEGF and HSP70.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystathionine γ Lyase Deletion Enhances Corpus Cavernosum Contraction via Thromboxane A₂ and Neurogenic Pathways Without Affecting Endothelial Function.","authors":"Tooyib A Azeez, Clifford J Pierre, Colin M Ihrig, Stephen P Chelko, Judy Muller-Delp, Justin D La Favor","doi":"10.1152/ajpregu.00133.2025","DOIUrl":"10.1152/ajpregu.00133.2025","url":null,"abstract":"<p><p>Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H₂S), a vasodilator critical for vascular function. While its systemic effects are well-documented, its role in erectile physiology remains unclear. This study investigated the impact of CSE deletion on vascular and erectile tissue reactivity. We hypothesized that CSE knockout (CSE-KO) mice would exhibit endothelial dysfunction. A total of 22 CSE-KO and 22 age-matched wild-type (WT) controls were studied at one year of age. The internal iliac artery (IIA), internal pudendal artery (IPA), and corpus cavernosum (CC) were harvested for <i>ex vivo</i> functional assessments using tissue, wire, and pressure myography. Vasoconstriction was evaluated using phenylephrine, endothelin-1, U-46619, and electrical field stimulation (EFS). Endothelium-dependent relaxation was assessed using acetylcholine (ACh) and flow-mediated dilation, while endothelium-independent relaxation was evaluated using sodium nitroprusside (SNP). Sodium sulfide (Na₂S) was used to assess H₂S-mediated dilation. Non-adrenergic, non-cholinergic (NANC) transmission was evaluated using EFS. No significant differences were observed in ACh-, SNP-, or flow-mediated relaxation, although CSE-KO mice demonstrated impaired NANC-nerve mediated relaxation in the CC. Moreover, CSE-KO mice exhibited significantly enhanced CC contraction in response to U-46619 and EFS, suggesting increased vascular resistance in the end organ CC rather than the pre-penile arteries. Histological analysis revealed no significant structural or fibrotic remodeling in any tissue, although there was a trend toward increased collagen deposition in the IIA and IPA. These findings indicate that chronic CSE deficiency does not impair endothelial function but alters neurogenic control and increases vasoconstrictive sensitivity specifically in the CC, potentially predisposing to erectile dysfunction.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-targeted dietary supplementation with fermentable fibers and polyphenols prevents hypobaric hypoxia-induced increases in intestinal permeability.","authors":"J Philip Karl, Heather S Fagnant, Patrick N Radcliffe, Marques Wilson, Anthony J Karis, Briony Sayers, Anisha Wijeyesekera, Glenn R Gibson, Harris R Lieberman, Grace E Giles, Jason W Soares","doi":"10.1152/ajpregu.00109.2025","DOIUrl":"10.1152/ajpregu.00109.2025","url":null,"abstract":"<p><p>Interactions between the gut microbiota and intestinal barrier may contribute to the pathophysiology of high-altitude illnesses. This study aimed to determine the effects of targeting the gut microbiota using dietary supplementation with a blend of fermentable fibers and polyphenol sources on gut microbiota composition, fecal short-chain fatty acids (SCFAs), and intestinal function and permeability during hypobaric hypoxia exposure. Healthy adults participated in a randomized, placebo-controlled, crossover study. Food products containing oligofructose-enriched inulin, galacto-oligosaccharide, high-amylose corn starch, cocoa, green tea and cranberry extracts, and blueberry powder (FP) or maltodextrin (placebo; PL) were consumed daily during three 2-wk phases separated by a ≥1-wk washout. During the final 36 h of each phase, participants resided in a hypobaric chamber simulating low (LA; 500 m) or high (HA; 4,300 m) altitude creating three experimental conditions: PL + LA, PL + HA, and FP + HA. Twenty-six participants completed ≥1 study phase and 13 [12 male; 21 ± 3 yr; body mass index (BMI) 25.4 ± 2.4 kg/m²] completed all three phases. Results demonstrated that FP mitigated hypoxia-induced increases in intestinal permeability within the small intestine and proximal colon while increasing <i>Bifidobacterium</i> relative abundance and decreasing gut microbiota α-diversity and colonic pH. Higher <i>Bifidobacterium</i> relative abundance and lower colonic pH were associated with greater reductions in intestinal permeability. However, FP did not alter fecal SCFA concentrations and increased gastrointestinal symptoms and altitude sickness during hypobaric hypoxia exposure. Findings suggest that targeting the gut microbiota with a combination of fermentable fibers and polyphenols can prevent hypobaric hypoxia-induced increases in intestinal permeability but that benefit does translate into a reduction in altitude illness symptoms.<b>NEW & NOTEWORTHY</b> Dietary supplementation targeting the gut microbiota may provide novel approaches to improving physiologic responses to environmental stressors such as those experienced during sojourn at high terrestrial altitudes. This study demonstrated that gut microbiota-targeted dietary supplementation using a blend of fermentable fibers and polyphenol sources can prevent hypobaric hypoxia-induced decrements in intestinal permeability. Findings support the emerging concept that the gut microbiota may be a modifiable factor influencing physiologic responses in austere environments.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R378-R399"},"PeriodicalIF":2.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}