Physiology最新文献

{"title":"Single-cell transcriptomics predicts colony stimulating factor-1 regulation of age-dependent intestinal epithelial restitution","authors":"A. Ziegler, Elizabeth C Rose, Jeremy Simon, Ismael Martinez, Courtney Deck, Scott Magness, Jack Odle","doi":"10.1152/physiol.2024.39.s1.2456","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2456","url":null,"abstract":"Intestinal diseases associated with ischemic injury, which damages the principal barrier against noxious luminal contents, result in unacceptably poor outcomes in newborns. Ischemia-induced loss of the intestinal epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. While this age-dependence in repair has not been demonstrated in traditional rodent models, we have developed a highly translational pig model of intestinal ischemic injury and repair that does reflect this difference. We have shown that, while juvenile (weaned) pigs recover rapidly after ischemic intestinal injury, barrier repair is markedly underdeveloped in neonatal (nursing) pigs due to complete failure of epithelial restitution. Importantly, we found that restitution in neonates can be rescued by the direct application of homogenized mucosa from ischemia-injured small intestine from juvenile pigs. The mechanisms that allow for this restitution and rescue remain to be defined. We hypothesized that by identifying a subpopulation of restituting enterocytes by their expression of cell migration transcriptional pathways, we can then predict novel upstream regulators of age-dependent restitution response programs. Superficial mucosal epithelial cells collected from recovering ischemic jejunum of juvenile pigs were processed for single cell RNA sequencing, unbiased clustering and upstream regulator analysis. A porcine intestinal epithelial cell line (IPEC-J2) and banked tissues from prior rescue experiments were qualitatively and functionally assessed for activity of predicted upstream regulators. Single cell transcriptomics in recovering juvenile epithelium revealed a subcluster of absorptive enterocytes that express several cell migration pathways key to restitution. Differentially expressed genes in this subcluster predicted their upstream regulation by many potential molecules, including colony stimulating factor-1 (CSF-1) which is known to induce cell migration in non-intestinal epithelial tissues. To begin validating this prediction, we demonstrated that CSF-1 was enriched in the ischemic juvenile mucosa which rescues neonatal restitution and documented expression of the CSF-1 receptor (CSF1R) in both neonatal and juvenile epithelium, indicating that these cells are equipped to respond to CSF-1. CSF-1 and CSF1R co-localized in ischemic juvenile, but not neonatal, wound-adjacent epithelial cells and in the restituted epithelium of juveniles and rescued (but not control) neonates. Further, the CSF1R inhibitor BLZ945 reduced restitution in scratch wounded IPEC-J2 cells. Single cell transcriptomics have the power to inform potential novel therapeutic targets, such as CSF-1, to improve mucosal recovery in neonates with intestinal failure in this unique and powerful pig mod","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141135473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Sexually Dimorphic Hepatic Cycle of Very Low Density Lipoprotein Uptake and Assembly","authors":"Tomaz Martini, Cedric Gobet, Andrea Salati, Jérôme Blanc, Aart Mookhoek, Graham Knott, Jessica Sordet-Dessimoz","doi":"10.1152/physiol.2024.39.s1.483","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.483","url":null,"abstract":"The liver shows striking sexual dimorphism, which is reflected in differences between women and men in pathologies inherently associated with hepatic function. Recent single-cell transcriptomes revealed spatiotemporal programmes of liver function on the sublobular scale. However, how sexual dimorphism affects this space-time logic remains poorly understood. To address this, we performed single-cell RNA-seq in the mouse liver, which allowed us to model how lobular position, circadian time and sex shape the transcriptome. We found that sex, space and time markedly influence xenobiotic detoxification and lipid processing, including lipoprotein metabolism. Crucially, the very low density lipoprotein receptor (VLDLR) is restricted to the pericentral zone, with significantly higher mRNA and protein levels in female mice. Using human samples, we were able to recapitulate both VLDLR's pericentral expression as well as higher mRNA and protein levels in premenopausal women compared to similarly aged men. In humans, we found that VLDLR expression depends not just on age but also body mass index. Conversely, several genes involved in VLDL assembly are periportally biased, and we corroborated periportal VLDL generation with electron microscopy, optimized for detecting low density lipid particles. Together, this suggests a hepatic cycle of periportal formation and pericentral uptake of VLDL. Crucially, these processes provide a new window into the sexual dimorphism characterizing differences in VLDL kinetics and atherosclerotic cardiovascular disease. The work was supported by a Swiss National Science Foundation grant. The authors declare no conflicting interests. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing changes to the skeletal muscle transcriptome of young and aged mice to young and aged humans in response to acute eccentric contractions","authors":"Bradley Gordon, Jake Boykin, Grant R. Laskin, Cynthia Vied","doi":"10.1152/physiol.2024.39.s1.1220","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1220","url":null,"abstract":"Resistance exercise alters several molecular events in skeletal muscle that change muscle size and function, including changes to the transcriptome. The signals altering the muscle transcriptome in response to resistance exercise remain ill defined. Defining those regulatory signals in muscle requires non-human models where manipulations can assess cause and effect. The electrically induced, unilateral eccentric contraction model of resistance exercise in rodents is widely used to mimic resistance exercise. However, the transcriptional changes that occur in response to eccentric contractions in the rodent model and the continuity of the rodent model to resistance exercise in humans are not well known. The purpose of this study was to define the transcriptional changes in skeletal muscle that occur in response to acute eccentric contractions in young and aged mice and define their continuity to transcriptional changes in the muscle of young and aged humans. Four-month-old and 24-month-old male C57BL/6 mice were subjected to a bout of electrically induced, unilateral eccentric contractions of the tibialis anterior (TA) muscle. RNA was isolated from the TA and subjected to RNA Sequencing. Lists of differentially expressed genes (DEGs) from the TA of young and aged mice were compared to RNA Sequencing datasets generated from the vastus lateralis muscle of young and aged humans following acute eccentric contractions. L andscape I n S ilico deletion A nalysis (Lisa) was used to predict the magnitude of transcription factor regulation of the DEGs. DEGs for mice or humans were categorized into age specific DEGs (specific to young or aged) or DEGs shared by both ages. The number of DEGs for mice or humans were distributed equally to each category, showing an age specific distribution that was conserved in both mice and humans. However, the DEGs in young and aged mice had very little overlap to the DEGs in young and aged humans. Only 113 DEGs were common across all ages and species. Interestingly, the relationship of transcription factors predicted to regulate DEGs between young and aged mice or young and aged humans was very strong. However, the relationship of transcription factors predicted to regulate DEGs of young mice and young humans or aged mice and aged humans was rather weak. In all, these data highlight the consistencies and differences in the muscle transcriptomic response to eccentric contractions. This work was supported in part by NIH R03AG073445 (BSG). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141137590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteric and Systemic Postprandial Lactate Shuttle Phases and Dietary Carbohydrate Carbon Flow","authors":"Robert G Leija, Casey C Curl, Jose Arevalo, Adam Osmond, Justin Duong, Melvin Huie, Umesh Masharani","doi":"10.1152/physiol.2024.39.s1.433","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.433","url":null,"abstract":"We interrogated the hypothesis of a Postprandial Lactate Shuttle (PLS) in young, healthy men and women (n=15). Participants reported to the lab (5:00 AM) following an overnight fast and had the forearm vein catheterized for primed continuous infusions of [6,6-2H]glucose and [3-13C]lactate stable isotope tracers. The contralateral hand vein was warmed and catharized for arterialized blood sampling. After a 90-minute (min) equilibration period participants underwent a 75 g oral glucose tolerance test (OGTT). Arterialized [lactate] rose from baseline (0.60sup>). We estimate carbon flow from the OGTT from the rates of appearance of glucose, lactate and GNG from lactate. At 120-min the 75 g load was accounted for as follows: 29 g as blood lactate, 24 g of glucose from hepatic glucose release, 8 g of glucose from GNG, and 14 g withheld in the liver. Because blood [lactate] and Ra rose before [glucose] and Ra, evidence of an Enteric PLS is provided. Because secondary increments in blood [lactate] and Ra coincided with those of glucose, results are interpreted to indicate presence of a larger, secondary Systemic PLS phase. Antiquated ideas of lactate production due to hypoxia in skeletal muscles need to be supplanted because glycolysis proceeds to lactate in fully aerobic tissues, and because dietary carbohydrate is processed via lactate shuttling. In humans, lactate is a major vehicle for carbohydrate carbon distribution and metabolis. NIH grant R01 AG059715. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age and Handgrip Strength Induce Differences in Micro- and Macro-Vascular Responses","authors":"Kyndall V Ransom, Miranda Traylor, Genevieve B Batman, Christian Cooper, Joshua Keller","doi":"10.1152/physiol.2024.39.s1.358","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.358","url":null,"abstract":"Purpose: Handgrip (HG) strength is a potent predictor of cardiovascular disease (CVD) and all-cause mortality. Advances in technology have provided novel assessments of peripheral microvascular and macrovascular health and function. These advances include measurements of skeletal muscle tissue oxygenation (StO2, %) with near-infrared spectroscopy (NIRS) during vascular occlusion tests (VOT) as well as carotid-femoral pulse-wave velocity (cfPWV), which is the current gold-standard to measure aortic stiffness. Although NIRS-VOT and cfPWV have been shown to change across the lifespan, it is unknown if these variables are sensitive to group differences as defined by HG strength. Therefore, our purpose was to examine mean differences in NIRS-VOT parameters and cfPWV between groups of low and high HG strength. We hypothesized that individuals with lower HG strength would exhibit lower vascular function. Methods: 67 adults were separated into age groups: young (19 – 40 yr), midlife (41 – 64 yr), and older (≥65 yr). Groups were divided into low and high strength at the median for HG strength, and quasi-balanced based on biological sex. This resulted in six participant groups (e.g., midlife low strength). The VOT included 3 min of rest, 5 min of ischemia, and 3 min of reperfusion to determine indices of reactive hyperemia. Indices included the initial (i.e., first 10 s) rate of re-saturation (upslope) and the maximal StO2 (StO2max) percent following ischemia. Aortic stiffness was defined as cfPWV using the time difference between the appearance of the carotid and femoral pulses. Separate 2×3 between factor (HG by Age Group) ANOVAs were conducted for each outcome. A p≤0.05 was considered significant, and data were presented as mean ± SD. Results: For upslope, there was a significant interaction (p=0.042, ηp2=0.078), and follow-up analyses revealed for young and midlife adults the high HG group exhibited greater upslopes than the low strength group (young: 2.24±0.9 vs. 1.64±0.7 and midlife: 2.21±0.9 vs. 1.59±0.7%∙s−1). There was no significant interaction (p=0.360) for StO2max, but there was a significant main effect (p<0.001) of Age such that it progressively decreased across the lifespan (83.9 ± 2.0 > 80.7 ± 2.3 > 77.3 ± 2.8%). Similarly, cfPWV exhibited a significant main effect (p<0.001; ηp2 =0.429) of Age indicating aortic stiffness worsened with age, independent of HG strength. Conclusions: These results indicated that upslope was sensitive to group differences in HG strength, but only in the young and midlife age groups. For StO2max and cfPWV, age differences appeared to elicit a stronger effect than HG strength. The current findings suggested that HG strength may be most reflective of a specific portion of the vascular tree, while the initial rate of re-saturation and StO2max may be influenced by different mechanisms associated with reactive hyperemia. Notably, the participants in this study were relatively healthy based on being free of any chronic","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141141531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardio-protective and Antioxidant Potential of Pterocarpus marsupium heartwood extract on Isoproterenol induced heart failure in rats","authors":"Bhawna Mattoo, Asmat Shamim, Iqbal Alam","doi":"10.1152/physiol.2024.39.s1.2253","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2253","url":null,"abstract":"Heart failure (HF) is a clinical syndrome characterised by a constellation of symptoms(dyspnea, orthopnea, lower limb swelling) and signs (elevated jugular venous pressure, pulmonary congestion) which have underlying cardiac abnormality resulting in reduced cardiac output and/or elevated intra-cardiac pressures. HF is a leading cause of mortality globally and despite major therapeutic advances, HF continues to cause substantial morbidity and mortality. Therefore, there is a need to develop new prophylactic and therapeutic strategies for HF. Isoproterenol (ISO) is a synthetic non-selective beta adrenoceptor agonist and is widely used to model toxic cardiomyopathy and heart failure. It induces myocyte damage mimicking myocardial infarction. In the present study, we used ISO to induce heart failure in Wistar rats and study the effect of Pterocarpus marsupium (PM) heartwood extract on it. PM is a well-recognised herbal drug known for its beneficial effect in diabetes with potential anti-inflammatory and anti-oxidative properties.Hypothesis: PM treatment will favourably modulate the cardiac hemodynamic, anti-oxidative stress and anti-inflammatory parameters compared to standard drug and control rats in isoproterenol induced heart failure rats.Methods & Results. Animals were randomly divided into 10 groups.1: Normal control rats fed normal pellet diet, 2: Normal control rats treated with Fluvastatin (10 mg/kg; oral gavage) for 15 days 3: Normal control rats treated with PM Extract (100 mg/kg; oral gavage) for 15 days. 4: Normal control rats subcutaneously injected with ISO {Heart Failure (HF) group} 5: HF rats treated with Fluvastatin (10 mg/kg; oral gavage) for 15 days. 6: HF rats treated with PM Extract (100 mg/kg; oral gavage) for 15days 7: HF rats treated with PM Extract (200mg/kg; oral gavage) for 15 days. 8: Rats pretreated with Fluvastatin (10 mg/kg; oral gavage) for 15 days and at the 15th day subcutaneously injected with ISO and continued Fluvastatin treatment for another 15 days 9: Rats pretreated with PM Extract (100 mg/kg; oral gavage) for 15 days and at the 15th day subcutaneously injected with ISO and continued PM Extract treatment for another 15 days 10: Rats pretreated with PM Extract (200 mg/kg; oral gavage) for 15 days and at the 15th day subcutaneously injected with ISO and continued PM treatment for another 15 days. The groups were compared pre and post treatment for cardiac hemodynamic parameters, anti- oxidative stress parameters (superoxide dismutase, nitric oxide, malondialdehyde nitric oxide), cardiac injury markers, anti-inflammatory parameters (Interleukin-6 and Tumor Necrosis Factor-α).The results of the present study indicate that prophylactic and therapeutic treatment PM heartwood extract improved the altered hemodynamic and biochemical parameters in isoproterenol-induced HF rats suggesting its cardio-protective action. None declared. This is the full abstract presented at the American Physiology Summit 2024 meeting and is","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coronary Vascular Rarefaction in Heart Failure","authors":"K. Fopiano, Davis J Hardell, Vijay S Patel, Z. Bagi","doi":"10.1152/physiol.2024.39.s1.2132","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.2132","url":null,"abstract":"Coronary vasculature rarefaction has been thought to play a role in the development of heart failure (HF), causing reduced myocardial perfusion; understanding the role that coronary rarefaction plays within HF presents an avenue for therapeutic strategies. We assessed the coronary microvascular and small vessel networks in left atrial appendage (LAA) samples to determine differences based on HF status. LAA samples were obtained from 15 consecutive patients during cardiac surgery (BMI: 22.8-37.9, age: 51-82, M:F: 9:6, NonHF:HF: 11:4). LAA samples were paraffn-embedded or flash frozen whereby 40 μm thick sections were then immunolabelled using DyLight 594 fluorescent tomato-lectin dye and z-stack images were rendered using microscopy. Z-stack images were input into Vesselucida360 and the vessel networks were three-dimensionally reconstructed via unbiased automatic tracing with multiple quantitative endpoints calculated. LAA samples were also used for proteomic analysis via LC-MS followed by statistical and pathway analyses to determine differences in protein expression and pertinent pathways as well as in a wide-scale gene expression array (NanoString) to further study underlying molecular targets. We found that the number of branching nodes and total vessel length in the coronary vascular network was decreased in HF compared to NonHF patients. Whereas the total volume and surface area were similar between HF and NonHF patients. Proteomic analysis and principal component analysis identified differences in protein profiles in the two groups, with pathway analysis identifying cardiac contraction and metabolism, along with hydrogen peroxide catabolic pathways downregulated in HF. Gene expression profiling identified numerous hypoxia response and oxidative stress response markers as downregulated in HF LAA samples. The data obtained show coronary vascular rarefaction occurring in HF patients, implying potential implications in the progression of HF. Additionally, proteomic data point to the downregulation of hydrogen peroxide response pathways as a potential mechanism for coronary microvascular rarefaction that we want to elucidate in future studies. T32 HL155011 (KAF) F31 NS132564 (KAF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Endothelin-1 on Resting Blood Pressure and the Blood Pressure Response to Hypoxia in Healthy Young Men","authors":"Anna Gonsalves, Sarah Baker, Dain W Jacob, Jennifer L Harper, Camila Manrique-Acevedo, Jacqueline Limberg","doi":"10.1152/physiol.2024.39.s1.1211","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1211","url":null,"abstract":"Objectives: Upregulation of endothelin-1 (ET-1) and its receptors have been linked to increases in hypoxic sensitivity of the carotid chemoreceptors and the development of hypertension. As such, chemoreflex sensitization has been shown in pre-clinical models to be attenuated by ET-1 receptor blockade. Herein, we sought to assess a role for ET-1 in the maintenance of resting blood pressure (BP) in healthy young men and determine whether chemoreflex control of BP could be altered by ET-1 blockade. We hypothesized endothelin receptor antagonism with oral bosentan would lower resting BP in healthy young men as well as the acute BP response to hypoxia. Methods: Twenty-four healthy young men (31±5 yrs, 26±3 kg/m2) completed two study visits (control, bosentan) separated by a minimum of 1 week. The nonspecific endothelin receptor antagonist bosentan (62.5 mg) was taken by mouth twice daily for 3 days prior to the second study visit. On each visit, beat-by-beat BP was assessed under 3 inspiratory air conditions: 1) steady-state normoxia (FiO2 0.21), 2) chemoreflex excitation produced by acute, graded hypoxia (FiO2 0.05 – 0.21), 3) chemoreflex inhibition elicited by transient hyperoxia (FiO2 1.00). Results: Oral bosentan treatment resulted in an increase in plasma ET-1 (0.9±0.9 to 1.3±0.6 pg/mL, p=0.004), supporting receptor blockade. Resting diastolic and mean BP were reduced following 3 days of bosentan treatment compared to control (diastolic: 73±5 to 69±7 mmHg, p=0.007; mean: 93±7 to 88±7 mmHg, p=0.005) with no change in systolic BP (p=0.507). Notably, the BP response to both acute hypoxia (-0.48±0.38 to -0.25±0.31 mmHg/%, p=0.004) and hyperoxia (main effect of bosentan, p=0.025) were attenuated following bosentan. Conclusions: Acute oral bosentan treatment resulted in a reduction in resting BP in healthy young men. The effect of endothelin receptor inhibition with bosentan further attenuated the rise in BP during chemoreflex excitation via acute, graded hypoxia as well as the fall in BP during chemoreflex inhibition (transient hyperoxia). Together these data support a role for ET-1 in control of resting BP in healthy young men, possibly through a chemoreceptor-mediated mechanism. NIH HL130339 (JL), Mayo Clinic Center for Biomedical Discovery (JL, SB). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141144409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sexual Effects of Testosterone on Mesenteric Arterial Reactivity in Ovariectomized Female Rats","authors":"Mohammad Moshiur Rahman, R. A. Islam, M. Razan, Mitra Esfandiarei, Melanie Felmlee, R. Rahimian","doi":"10.1152/physiol.2024.39.s1.1648","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1648","url":null,"abstract":"The number of transgender individuals is on the rise in the United States. Although there are studies on the effects of sex hormones on cardiovascular function of cisgender male and female, still much is not known about the effects of cross-sex hormone therapy (CSHT) on cardiovascular function in transgender individuals. It has been shown that the risk factors of cardiovascular diseases (CVD) are increased in transgenders after they undergo CSHT. Epidemiological studies suggest that transgender females (male to female, MtF) on estrogen therapy develop higher risk of CVD compared to transgender males (female to male, FtM) taking testosterone. This study investigates the effects of testosterone or estrogen treatment on the third branch of mesenteric arterial reactivity in ovariectomized female rats. Briefly, 8-10 weeks old female Sprague Dawley (SD) rats were ovariectomized (OVX) and subcutaneously implanted with placebo (OVX + PL) or testosterone (OVX + T, 7.5 mg) or 17β- estradiol (OVX + E2, 1.5 mg) pellets for about 35 days. Age matched intact female SD rats were also included in the experimental groups. Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh) was measured in the precontracted mesenteric arteries with phenylephrine (PE), using wire myography. Responses to sodium nitroprusside (SNP)-induced vasorelaxation, and PE- and endothelin-1 (ET-1) induced vasocontraction were also determined. We demonstrated that the responses to ACh in rat mesenteric arteries were not altered by either ovariectomy or estrogen treatment. However, testosterone treatment of OVX female rats significantly enhanced the sensitivity to ACh-induced vasorelaxation compared with those in other experimental groups. Moreover, the mesenteric arteries of OVX + T exhibited a trend of reduced sensitivity to PE responses compared to other groups. Furthermore, the maximum tension to ET-1 was significantly reduced in mesenteric arteries of OVX + T compared to OVX+E2 and OVX+PL groups. The vasorelaxation responses to SNP were not altered in any of experimental groups studied. These data suggest that elevated sensitivity to ACh in testosterone-treated ovariectomized female rats might be, in part, due to reduced vessel responses to contractile agents, but not altered sensitivity of smooth muscle to nitric oxide (NO) in this group. Additional studies are needed to investigate the underlying mechanisms and document the consequences for the improvement of EDV observed in OVX + T rats. NIDA/NIGMS, 1SC1DA052120-01 to MF, Bridge Grant from University of the Pacific to RR. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing Confidence in the HPV Vaccine","authors":"Madison Bordenave","doi":"10.1152/physiol.2024.39.s1.1410","DOIUrl":"https://doi.org/10.1152/physiol.2024.39.s1.1410","url":null,"abstract":"HPV causes approximately 26,600 new cancer cases every year in the United States. HPV vaccination initiatives have helped lower HPV infection rates. However, vaccination rates still remain incredibly low. Less than 40% of adolescents that qualify for vaccination have completed a full series. Community engagement through focus groups, interviews, pre and post online surveys of parents have been shown to improve attitudes toward vaccinations. This is a qualitative cross-sectional survey using both quantitative and non-numerical data collected through interviews in order to further understand the reasoning of HPV vaccine hesitant parents who decide to either opt out of vaccination or fail to complete the vaccine series. The study seeks to implement educational strategies such as the testing of a website that works to close the information gap, the amount of available knowledge regarding HPV vaccination compared to the level of knowledge parents actually have. These strategies are implemented with the goal of addressing the concerns of vaccine hesitant parents and assessing their level of hesitancy before and after providing the requisite information regarding HPV vaccination through the interview process. The goal of this study is to both educate and aid in parents decision making when deciding to vaccinate their children for HPV. There is limited community based research available on HPV vaccination hesitancy amongst parents. The approach of using educational materials along with a webpage is new in addressing vaccine hesitancy with regards to HPV. This research could help increase HPV vaccination rates in order to lower HPV related cancers in the future. We found that knowledge played a critical role in improving attitudes toward the HPV vaccine and that improving the knowledge quality of vaccine participants may improve vaccination rates. This work was supported by the American Cancer Society. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141130670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}