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

{"title":"Moderate intermittent hypoxic conditioning to enhance cerebrovascular function in the elderly: a randomized controlled trial.","authors":"Hugo Randy, Titouan Paul Perrin, Abdallah Ghaith, Dario Kohlbrenner, Patrice Flore, Benoit Champigneulle, Michel Francois Guinot, Stéphane Doutreleau, Samuel Verges, Julien V Brugniaux, Mathieu Marillier","doi":"10.1152/ajpregu.00160.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00160.2025","url":null,"abstract":"<p><p><b>Background:</b> Aging is associated with cerebrovascular impairment, increasing the risk for neurovascular and degenerative diseases. Intermittent hypoxic conditioning (IHC) has been proposed as a valuable strategy to enhance vascular health. However, its effects in cerebrovascular territories remains unclear, particularly in older adults. <b>Methods:</b> Eighteen elderly individuals (62-79 years, 11 males) were randomly assigned to either an IHC (n=8) or control group (CTL, n=10). Both groups underwent 24 sessions (3 sessions/week) of passive moderate exposure to either intermittent hypoxia (targeted oxygen saturation by pulse oximetry= 75-80%) or sham hypoxia. Middle cerebral artery (MCA) reactivity to hypo- (hyperventilation task) and hypercapnia (carbon dioxide ramp administration) was assessed using transcranial doppler ultrasound. Cerebrovascular reactivity to carbon dioxide (CVR_CO2) was evaluated in both absolute and relative changes in MCA blood velocities (MCAv), before (Pre), 3-4 days after (Post 1) and 2 months after (Post 2) intervention cessation. <b>Results:</b> As expected, MCAv decreased during hypocapnia (CTL= -15.7±7.0 cm/s; IHC= -15.9±6.0 cm/s) and increased during hypercapnia (CTL= 20.7±8.4 cm/s; IHC= 18.2±11.1 cm/s) at all time points in both groups. However, compared to CTL, IHC did not significantly improve any CVR_CO2 parameters (e.g., relative CVR_CO2 to hypercapnia, Pre: CTL= 4.3±1.9, IHC= 3.1±2.0; Post 1: CTL= 4.1±1.6, IHC= 3.4±1.6; Post 2: CTL= 4.7±2.0, IHC= 3.5±1.7 cm/s/mmHg; <i>p</i>=0.739). <b>Conclusion:</b> The present work does not support the potential benefits of IHC on cerebrovascular function. However, future studies are required to confirm these preliminary results and may consider a more comprehensive appraisal of the cerebral hemodynamic control.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336371","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":"Slow-twitch oxidative myofiber proportions and capillary number per myofiber are reduced in growth-restricted fetal sheep.","authors":"Tristan B Dear, Eileen I Chang, Saif Al-Juboori, Jane Stremming, Stephanie R Wesolowski, Sonnet S Jonker, Paul J Rozance, Evgenia Dobrinskikh, Laura D Brown","doi":"10.1152/ajpregu.00044.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00044.2025","url":null,"abstract":"<p><p>Pregnancies affected with placental insufficiency and fetal growth-restriction (FGR) are characterized by reduced umbilical blood flow, decreased nutrient and oxygen supply to the fetus, and impaired fetal skeletal muscle growth. Vascular development within FGR skeletal muscle has not been well described. We hypothesized that chronic placental insufficiency impairs microvascular architecture in FGR fetal skeletal muscle, resulting in decreased vascularity. We used a sheep model of placental insufficiency induced FGR by exposing pregnant ewes to elevated temperature. Four muscles from the hindlimb were obtained in late gestation from FGR and control fetal sheep for histological and molecular analysis. The proportion of slow-twitch oxidative fibers was 22% lower in the tibialis anterior (TA) and 32% lower in the extensor digitorum longus (EDL) muscles in FGR fetuses compared to controls. Total cross-sectional area was 20-45% lower in biceps femoris (BF), TA, EDL, and soleus (SOL) muscles. The capillary number per myofiber was 34% lower in BF, 51% lower in TA, and 21% lower in SOL FGR muscles compared to controls. Capillary area was also 44% lower in the FGR TA muscle. Taken together, late gestation fetuses with placental insufficiency induced FGR had smaller myofibers, fewer slow-twitch oxidative myofibers, and defects in angiogenesis and capillary formation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336449","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":"Resting beat-to-beat blood pressure variability is preserved in young adults with major depressive disorder.","authors":"Ashley M Darling, Benjamin E Young, Cynthia M Dominguez, Jeremiah A Joseph, Paul J Fadel, Erika F H Saunders, Jody L Greaney","doi":"10.1152/ajpregu.00174.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00174.2025","url":null,"abstract":"<p><p>Major depressive disorder (MDD) often first emerges during young adulthood and is associated with an increased risk of future hypertension, but our understanding of blood pressure (BP) regulation in young adults with MDD who are otherwise clinically healthy remains limited. We tested the hypothesis that beat-to-beat BP variability (BPV) would be greater in young unmedicated adults with MDD compared to non-depressed healthy adults (HA). Because the arterial baroreflex is essential for beat-to-beat BP regulation, we also hypothesized that (1) sympathetic baroreflex sensitivity would be reduced in young adults with MDD and (2) positively related to BPV. Beat-to-beat BP (finger photoplethysmography), heart rate (ECG), and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were measured during 10-20-min of supine rest in 40 young adults with MDD (unmedicated; n=19 female; 113±9/74±6 mmHg) and 27 HA (n=17 female; 116±10/73±6 mmHg). There were no group differences in either resting BP (116±10/73±6 HA vs. 113±9/74±6 mmHg MDD; both p>0.05) or MSNA (26±11 vs. 24±13 bursts/100 heartbeats MDD; p=0.50). Neither beat-to-beat BPV (e.g., systolic BP standard deviation: 5.8±2.1 HA vs. 5.9±1.6 mmHg MDD, p=0.47) nor sympathetic baroreflex sensitivity (e.g., burst incidence gain: -3.8±1.3 HA vs. -3.4±1.5 bursts/100 beats/mmHg MDD, =0.34) were different in MDD compared to HA. In adults with MDD, sympathetic baroreflex sensitivity was related to BPV (<i>r</i>=0.52, p=0.01). Traditional measures of beat-to-beat CO and TPR variability were likewise not different between groups (all p>0.05). These data demonstrate that both beat-to-beat BPV and sympathetic baroreflex sensitivity are preserved in young unmedicated adults suffering from MDD.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336363","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":"Nonphotic Entrainment and Phase-Shifting of Circadian Rhythms by Novelty-Induced Wheel Running in Female Mice.","authors":"Ren Y Sato, Yujiro Yamanaka","doi":"10.1152/ajpregu.00194.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00194.2025","url":null,"abstract":"<p><p>Environmental light-dark (LD) cycles serve as the primary zeitgeber for the mammalian circadian system, but scheduled physical activity such as voluntary wheel running can act as a potent nonphotic cue. Previous studies on nonphotic entrainment have predominantly used male animals, leaving sex-specific mechanisms largely unexplored. In this study, we investigated circadian behavioral entrainment and phase-shifting responses to scheduled wheel-running activity in female C57BL/6J mice under constant darkness (DD). Mice underwent scheduled daily exposure to a novel cage with a running wheel (NCRW) for 3 hours, and spontaneous locomotor rhythms were analyzed before, during, and after exposure. Fifteen of 16 female mice achieved steady-state entrainment when the NCRW schedule coincided with activity onset. However, they lacked both anticipatory behavior and behavioral after-effects of entrainment-defined as persistent changes in circadian period and activity timing following entrainment-unlike what has been previously reported in males. To interpret entrainment dynamics, we constructed phase response curve (PRC) for a single 3-hour pulse of exposure to NCRW in both sexes. Female PRC displayed prominent delay portions in the late subjective day and early subjective night, contrasting with male profiles showing minor advances in the same windows. These findings reveal a sex difference in nonphotic circadian entrainment and suggest that underlying mechanisms, including oscillator coupling or differential sensitivity to nonphotic stimuli, may vary between males and females. The results emphasize the importance of considering biological sex in circadian research and provide a basis for further investigation into sex-specific regulation of behavioral rhythms.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336422","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":"Effect of controlling CO₂ on peripheral hypercapnic chemosensitivity at exercise intensities above the respiratory compensation point.","authors":"Aaron J Thompson, Armando Riojas, Paolo B Dominelli","doi":"10.1152/ajpregu.00165.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00165.2025","url":null,"abstract":"<p><p>A rapid change in arterial CO₂ tension causes changes in ventilation, referred to as peripheral hypercapnic chemosensitivity (PHC). The PHC increases from rest to low-intensity exercise yet is not further augmented at higher exercise intensities, where additional ventilatory stimulants are present. During supra-respiratory compensation point (RCP) exercise, as arterial CO₂ tension falls, so does PHC, which may mask the effect of other ventilatory stimuli. Twenty healthy subjects (<i>n</i>=10 females) completed a maximal exercise test and on subsequent days (2 and 3) had PHC measured at rest, 40% of maximal work rate (Wmax), and supra-RCP exercise intensities. On one experimental day, participants were kept isocapnic, and on the other, end-tidal carbon dioxide (P_ETCO₂) declined naturally during supra-RCP exercise (poikilocapnia). PHC was measured as the quotient between the change in ventilation and P_ETCO₂ after two breaths of hypercapnic (10% CO₂) gas delivered 3-5 times during each condition. There was a significant increase in PHC during supra-RCP intensities with isocapnia, compared to poikilocapnic exercise (+11.2±6%) (<i>p</i>=0.0015). Yet during the isocapnia day, there was still no significant increase in PHC from 40% intensity to supra-RCP (<i>p</i>=0.96). A repeated measures correlation demonstrated a significant relationship between PHC and P_ETCO₂ during poikilocapnia (<i>r</i>=0.49, <i>p</i><0.001), with no significant relationship during isocapnia (<i>r</i>=0.06, <i>p</i>=0.57). We conclude that the metabolic milieu associated with supra-RCP exercise does not impact PHC and there is a CO₂-dependent relationship in which P_ETCO₂ influences PHC independent of the initial exercise sensitization.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312163","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":"Inulin Alleviates Intestinal Barrier Dysfunction Induced by Chronic Intermittent Hypoxia by modulating intestinal microbiota in Mice.","authors":"Yu Xue, Ruonan Tang, Zanhua Liu","doi":"10.1152/ajpregu.00156.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00156.2025","url":null,"abstract":"<p><p><b>Background:</b> Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), disrupts intestinal barrier function and alters gut microbiota composition, leading to systemic inflammation and metabolic disorders. <b>Objective:</b> To investigate the protective role of inulin in mitigating CIH-induced intestinal barrier dysfunction and systemic inflammation in mice, with a focus on the underlying gut microbiota-mediated mechanisms. <b>Methods:</b> C57BL/6J mice were exposed to CIH for 10 weeks with or without inulin supplementation. Intestinal permeability, tight junction protein expression, inflammatory cytokine levels, and gut microbiota composition were assessed by FITC-Dextran assay, ELISA, RT-qPCR, western blotting, H&E staining and 16S rRNA sequencing. The role of gut microbiota was evaluated using antibiotic intervention. <b>Results:</b> Inulin significantly reduced permeability of intestines, restored protein expression of TJ, and alleviated histological damage. It lowered transforming growth factor-β, tumor necrosis factor-α, interleukin (IL)-23, -6 and 1β, IL-6 levels, while increasing IL-10. Inulin reversed CIH-induced gut dysbiosis, increased microbial diversity, and modulated the <i>Firmicutes/Bacteroidetes</i> ratio. Antibiotic treatment confirmed microbiota-dependent effects. <b>Conclusion:</b> Inulin mitigated dysfunction of intestinal barrier that was induced by CIH and systemic inflammation through modulation of gut microbiota, thus highlighting its potential as a dietary intervention for OSA-related complications.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297769","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":"Irisin deficiency exacerbates cardiac dysfunction and enhances hemorrhage injury in hemorrhage/resuscitation.","authors":"Supaporn Kulthinee, Lijiang Wang, John Slate-Rmano, LingNa Huang, Thomas Zhao, Patrycja M Dubielecka, Jia-Qiang He, Shougang Zhuang, Ting C Zhao","doi":"10.1152/ajpregu.00013.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00013.2025","url":null,"abstract":"<p><p><b>Background:</b> Irisin contributes critically to modulating metabolism and tissue survival in muscles and adipocytes. Whether deficiency of irisin impacts the hemorrhagic injury and/or whether the effect of irisin deficiency on hemorrhagic injury primarily relies on Irisin, which is currently unknown. <b>Objectives:</b> We utilize irisin knockout mouse to eliminate Irisin and pharmacological approaches in mouse hemorrhagic model to determine the function of Irisin on hemorrhage and resuscitation (H/R). <b>Methods:</b> Hemorrhage was induced by achieving a mean arterial blood pressure of 35-45 mmHg for 60 minutes followed by two hours of resuscitation in mice. Experimental groups were divided as the following (n=6-8/per group): Sham group <i>I and II:</i> Wild type (WT) mice and <i>Irisin</i>-KO mice were subjected to femoral catheterization without H/R; Groups <i>III</i> and <i>IV:</i> WT mice and <i>Irisin</i>-KO mice were subject to H/R, respectively; Groups <i>V and VI:</i> Irisin (50μg/kg, i.v.) was infused into WT and <i>Irisin-KO</i> H/R mice during resuscitation. Mean blood pressure, myocardial function, serum cytokine, inflammatory cell infiltration, and TUNEL positive apoptosis, active caspase 3, components of oxidative phosphorylation and mitochondrial ATPase activity in muscles were determined. <b>Results:</b> Irisin deficiency exacerbated cardiac dysfunction in H/R in association with increases in IL-6, the infiltration of inflammatory cells, active caspase-3 and reduced oxidative phosphorylation OXPHOS) and ATPase activities. The effects of Irisin deletion on H/R was rescued by Irisin. <b>Conclusion:</b> Deletion of Irisin exacerbated injury of H/R, which was rescued by infusion of Irisin, suggesting a key role of Irisin in the regulation of hemorrhage/resuscitation.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297775","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 Pharyngeal Phase of Swallowing Controls Deglutitive Inhibition.","authors":"Ivan M Lang, Bidyut K Medda, Francis Edeani, Reza Shaker","doi":"10.1152/ajpregu.00136.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00136.2025","url":null,"abstract":"<p><p>The goal of this study was to determine which phase of swallowing causes deglutitive inhibition (DI). DI is inhibition of ongoing peristalsis by a new swallow. <b>Methods:</b> Pharynx and esophagus of decerebrate cats (N = 25) were instrumented to record esophageal peristalsis. Injecting saline into pharynx or esophagus activated primary (pharyngeal and esophageal phases) peristalsis repeatedly and randomly, or secondary (esophageal phase) peristalsis once, respectively. <b>Results:</b> When a new primary peristalsis occurred during ongoing primary peristalsis, the occurrence of ongoing esophageal peristalsis was blocked when it was 1 - 10 cm from upper esophageal sphincter, then secondary peristalsis occurred 1.3 ± 0.1 s (N = 22) later at same location. This esophageal blockade occurred almost simultaneous (0.15 ± 0.01 s (N = 17) before) with activation of thyropharyngeus activation during the new pharyngeal phase. When ongoing primary peristalsis was at or below 13 cm from upper esophageal sphincter, the magnitude of primary esophageal peristalsis significantly decreased (102 ± 14 vs 49 ± 8 mm Hg, N=8, P < 0.01) during the new pharyngeal phase, but peristaltic progression was not altered. DI had same effects on secondary peristalsis. DI of ongoing peristalsis in distal esophagus occurred before or without new esophageal phase in every case (21 cases, N = 9), but one. <b>Conclusions:</b> DI is central inhibition of ongoing esophageal phase of swallowing by the new pharyngeal phase as short-term cessation of striated muscle peristalsis and longer-term reduction in smooth muscle peristaltic magnitude. Esophageal or oral phase of swallowing does not cause DI.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290752","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":"Peripheral Catecholamine Systems: An Evolutionary Perspective.","authors":"David S Goldstein","doi":"10.1152/ajpregu.00169.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00169.2025","url":null,"abstract":"<p><p>This essay examines in evolutionary perspective body systems outside the brain that use the catecholamines dopamine (DA), norepinephrine (NE), and epinephrine (EPI) as chemical messengers. Peripheral catecholaminergic systems represent three principal mechanisms by which the brain regulates functions of body organs. DA serves as an autocrine-paracrine factor in the kidneys and splanchnic organs, NE is the neurotransmitter of the sympathetic noradrenergic system (SNS), and EPI is the main hormone secreted by adrenomedullary chromaffin cells. Comparative physiological data suggest that the DA autocrine-paracrine system emerged first, followed by noradrenergic nerve networks culminating in the SNS, with the hormonal sympathetic adrenergic system (SAS) appearing most recently. Examples are presented of the diverse ways these catecholamines have been used during evolution, although the ecological niches that conferred selective advantages remain uncertain. The discussion addresses catecholamine receptors, co-transmission, and interactions between catecholaminergic, neuroendocrine, and immune systems. In humans, the transition to bipedalism likely promoted SNS adaptations for orthostatic regulation of cardiac output as well as for sodium homeostasis and temperature control. The roles of the SAS in organism-wide stress responses, distress, and sympathoadrenal imbalance in fainting are also considered. Concepts such as antagonistic pleiotropy, allostatic load, and autotoxicity are discussed in relation to aging-associated diseases that feature catecholaminergic neurodegeneration. Understanding the phylogeny of peripheral catecholaminergic systems may provide a foundation for Darwinian medicine.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285335","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":"Selective upregulation of VEGF receptor 2 normalizes maternal and fetal outcomes in a rat model of preeclampsia.","authors":"Jacqueline Novak, Brittany A Balser, Yang H Yun, Rolando J J Ramirez","doi":"10.1152/ajpregu.00079.2024","DOIUrl":"https://doi.org/10.1152/ajpregu.00079.2024","url":null,"abstract":"<p><p>Preeclampsia is the leading cause of maternal and fetal morbidity and mortality in the United States. Maternal hypertension occurs to increase blood perfusion but it is inadequate, resulting in growth-restriction. Improving placental perfusion could alleviate maternal hypertension and improve fetal outcomes. An imbalance between vasodilators and vasoconstrictors mediates the pathophysiology of preeclampsia shifting the balance towards vasodilation would be beneficial for maternal and fetal outcomes. Our hypothesis is that increasing the VEGFR2 receptors in the uterine tissue will improve the pathophysiology of preeclampsia. To test our hypothesis, we used the reduced uterine perfusion pressure rat model (RUPP) and treatment with non-viral LTP nanoparticles containing the plasmid DNA for VEGFR2. The LTP nanoparticles are administered in one dose at gestational day 14 (same day as surgery). Maternal blood pressure, measured at gestational day 21 in anesthetized rats, mean arterial pressure was decreased in the RUPP rats treated with LTP-VEGFR2 nanoparticles (72.8±3.6mmHg) compared to control RUPP (100±6mmHg, p=0.01). In addition, myogenic reactivity of uterine arteries isolated from RUPP treated with LTP-VEGFR2 demonstrated decreased myogenic reactivity compared to RUPP. At the 120mmHg pressure step, arteries from RUPP treated with LTP-VEGFR2 nanoparticles increased in diameter by 42±12% compared to a decrease of 22±5% in untreated RUPP (p=0.003). The role for the VEGF myogenic studies was confirmed with VEGF neutralizing antibodies. In addition, treatment with LTP-VEGFR2 nanoparticle treatments increased fetal and placental weights in RUPP rats. This study demonstrates that overexpression of VEGFR2 by LTP nanoparticles may provide a novel therapeutic agent for the treatment of preeclampsia.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285372","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}