Physiology最新文献

{"title":"Sex-specific impact of aging on muscle sympathetic neural discharge patterns during incremental rhythmic handgrip exercise","authors":"Andrew W D'Souza, Ryosuke Takeda, Kazumasa Manabe, S. Hissen, Geoff B Coombs, Takuro Washio, Belinda Sanchez, Qi Fu, K. Shoemaker","doi":"10.1152/physiol.2023.38.s1.5730359","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5730359","url":null,"abstract":"Sex-disparities exist in the risk of developing hypertension throughout the lifespan, with a greater prevalence of hypertension amongst postmenopausal females compared to similarly aged males. Though the underlying mechanisms are multifactorial, exaggerated sympathetic neuro-cardiovascular reactivity may be an important contributor. Indeed, postmenopausal females exhibit exaggerated exercise pressor responses compared to young adults, and older males. However, the interactive effects of age and sex on muscle sympathetic nerve activity (MSNA) and action potential (AP) coding patterns during exercise remains unclear. We hypothesized that older females would exhibit the greatest increase in MSNA and AP recruitment during exercise and post-exercise circulatory occlusion (PECO) relative to young males and females, as well as older males. MSNA and AP discharge patterns (microneurography and continuous wavelet transform) were assessed in 12 young males (YM (mean±SD); 26±4, years), 11 young females (YF; 25±4 years), 11 older males (OM; 71±11 years), and 12 older females (OF; 71±4 years) during incremental rhythmic handgrip exercise to fatigue followed by 2 minutes of PECO. At peak exercise, OM demonstrated a smaller change from baseline (Δ) in MSNA burst incidence (BI) compared to all other groups (YM: Δ8±9, YF: Δ9±8, OM: Δ-6±8, OF: Δ6±7 bursts/100heartbeats; all ANOVA post-hoc P<0.05), whereas ΔMSNA burst frequency (BF), Δburst amplitude (BA), and Δtotal activity were not different between groups (all P>0.05). Conversely, YM demonstrated greater ΔAPs/burst (YM: Δ5±3, OM: Δ0.4±3, OF: Δ2±2 APs/burst; post-hoc P<0.05) and ΔAP clusters/burst (YM: Δ2±1, OM: Δ0.1±1, OF: Δ0.7±0.7 Clusters/burst; post-hoc P<0.05) compared to OM and OF, but not compared to YF (Δ2±3 APs/burst and Δ0.9±0.8 clusters/burst; both P≥0.07). However, no group differences were observed in the recruitment of larger axons (YM: Δ6±2, YF: Δ4±2, OM: Δ2±5, OF: Δ4±3 clusters; P=0.33). Contrary to exercise, group-by-time interactions existed during PECO for ΔMSNA BF ( P<0.01), ΔBI ( P<0.01), and Δtotal activity ( P<0.01) where greater increases occurred during the first minute of PECO in young compared to older adults (all post-hoc P<0.05), whereas in the final minute of PECO, MSNA ΔBF and ΔBI were only greater in YM compared to OM and OF (all P<0.05), and total activity was greater in YM and YF compared to OF only (all P<0.05). No group-by-time interactions were observed for ΔMSNA BA ( P=0.37), ΔAPs/burst ( P=0.94), ΔAP clusters/burst ( P=0.95) or Δtotal AP clusters ( P=0.41) during PECO. Altogether, MSNA and AP reactivity during exercise was not exaggerated in OF, but age-related reductions in AP recruitment were observed in males. During PECO, MSNA responses were lower in older relative to young adults but, AP recruitment was unaltered by age. Thus, exaggerated MSNA or AP reactivity may not explain the greater prevalence of hypertension in OF. Supported by the Natural Sciences and Engineering","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"123 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77857504","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":"Senolytics reduce endothelial cell DNA damage and telomere dysfunction in old age","authors":"Samuel I. Bloom, Eric Tuday, M. Islam, V. Gogulamudi, L. Lesniewski, A. Donato","doi":"10.1152/physiol.2023.38.s1.5733289","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5733289","url":null,"abstract":"Aging results in an accumulation of cellular damage that activates tumor suppressor pathways leading to permanent cell cycle arrest known as cellular senescence. Damage to DNA is a robust inducer of cellular senescence. Furthermore, repeat DNA sequences at the ends of chromosomes known as telomeres are particularly susceptible to damage that leads to senescence. Senescent cells adopt a pro-oxidative, pro-inflammatory phenotype that often adversely impacts the local tissue milieu. Senolytics are drugs that specifically induce cell death in senescent cells. Senolytic drugs have been shown to delay or reduce a multitude of age-related diseases in pre-clinical studies and are currently under investigation for use in clinical trials in humans. Many senolytic drugs were originally discovered based on their ability to induce cell death in senescent endothelial cells in cell culture. However, a key unanswered question is whether this phenomenon occurs in vivo. This is critical to understand because endothelial cell senescence contributes to both cardiovascular and metabolic diseases. In the present study, we tested the hypothesis that chronic administration of a senolytic cocktail will reduce the burden of endothelial cell senescence, as well as other molecular hallmarks of aging, including DNA damage and telomere dysfunction. To test this hypothesis, we treated 21-month-old mice (N = 10 / group) with the senolytic drug cocktail dasatinib (D, 5 mg/kg body mass) and quercetin (Q, 50mg/kg body mass) on three consecutive days every two weeks for three months via oral gavage. Control mice were treated with vehicle control (10% polyethylene glycol 4000 solution). At 24 months of age, carotid artery endothelial cell mRNA was isolated and expression of the cyclin-dependent kinase inhibitor that enforces senescence known as p21 was reduced in D+Q treated compared to vehicle-treated mice (p < 0.05). Additionally, lungs from 10 mice per group were collected and pooled, CD31+ lung endothelial cells were isolated and cultured briefly, and ~267 cells per group were examined. Immunofluorescence for the DNA damage marker 53BP1 demonstrated that treatment with D+Q reduced the percentage of endothelial cells with DNA damage (p < 0.05). We also performed immunofluorescence-fluorescent in situ hybridization to detect the abundance of 53BP1 foci colocalized to telomeres, a measure of telomere-specific damage known as telomere dysfunction-induced foci (TIF). Treatment with D+Q reduced the percentage of endothelial cells containing TIF (p < 0.05). Taken together, these data demonstrate that treating aged mice with D+Q reduces endothelial cell senescence likely in part by clearing cells that have accumulated DNA damage and dysfunctional telomeres. National Institutes of Health Awards R01 AG048366 (LAL), R01 AG060395 (AJD), 5K08AG070281 (ET), 1F31AG076312 (SIB). Veteran's Affairs Merit Review Award I01 BX004492 (LAL) from the United States (U.S.) Department of Veterans Affairs ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"44 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80070223","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":"Augmented sympathetic neurovascular transduction following acute exercise in normotensive adults","authors":"Massimo Nardone, Kathryn Pfundt, Philip J. Millar","doi":"10.1152/physiol.2023.38.s1.5732355","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732355","url":null,"abstract":"Introduction: The effects of an acute bout of aerobic exercise on sympathetic neurovascular interactions in normotensive adults remain unclear. Pharmacological work has previously demonstrated unchanged α-adrenergic receptor sensitivity, however, assessments under closed-loop conditions have not been conducted. The objective of the current study is to evaluate sympathetic neurovascular transduction following acute exercise in normotensive adults. We hypothesize that acute exercise will decrease sympathetic neurovascular transduction. Methods: Using a randomized cross-over design, eight young healthy participants (four female) performed either: 1) 60 minutes of cycling exercise at 60% VO2max, or 2) 60 minutes of a seated control, separated by a minimum of 1-month. Ninety minutes following both interventions, a 10-minute neuro-cardiovascular assessment was preformed in the supine position. Beat-to-beat heart rate (electrocardiography), blood pressure (finger photoplethysmography), muscle sympathetic nerve activity (MSNA; fibular nerve microneurography), and superficial femoral artery blood flow (Duplex ultrasound) were quantified; femoral vascular conductance (FVC) was calculated as blood flow/mean arterial pressure. Sympathetic-FVC transduction was quantified using the signal-averaging technique, whereby FVC responses to each MSNA burst were serially tracked over 15 cardiac cycles and averaged to derive the nadir change in FVC. Lastly, following measurements performed on the control visit, a subset of participants (n=4) submerged the lower limb into 40°C water to the level of the malleolus, to assess sympathetic-FVC transduction following acute increases in skin blood flow. Results: Compared to control, heart rate (60±8 vs. 66±8 beats/min), superficial femoral artery blood flow (68±25 vs. 104±42 mL/min), and femoral vascular conductance (0.9±0.3 vs. 1.4±0.5 mL/min/mmHg) were elevated following exercise (all P<0.02), while mean arterial pressure (76±4 vs. 78±7 mmHg; P=0.41) and MSNA burst frequency (18±6 vs. 18±5 bursts/min; P=0.85) were not different. The reduction in FVC following a sympathetic burst was increased following exercise (-0.12±0.04 vs. -0.17±0.06 mL/min/mmHg; P=0.04). A greater increase in FVC following exercise was associated with greater magnitude increase in sympathetic-FVC transduction (r=-0.65; P=0.08). However, the increase in FVC following lower limb heating (0.9±0.3 vs. 2.1 mL/min/mmHg; P<0.01) was not associated with parallel changes in sympathetic-FVC transduction (-0.07±0.04 vs. -0.07±0.04 mL/min/mmHg; P=0.92). Conclusion: Sympathetic-FVC transduction is acutely elevated following aerobic exercise, which was associated with the magnitude of post-exercise vasodilation. Considering that sympathetic-FVC transduction was unchanged during lower limb heating, these preliminary observations suggest that augmented sympathetic neurovascular transduction is facilitated by a blood flow-independent mechanism. This research was support","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"34 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80116887","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":"Assessing multiple-choice questions based on language precision and best practices to promote equity in the Dental Physiology course","authors":"M. Lopez","doi":"10.1152/physiol.2023.38.s1.5731455","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5731455","url":null,"abstract":"Student assessment in professional schools is conducted mainly through examinations based on multiple-choice questions (MCQs). Although grading this type of assessments saves time, questions that are not well-written may impact students’ performance. Technical flaws in MCQs include those that provide irrelevant difficulty and those that provide an advantage to test-wise examinees. In addition, MCQs with these flaws may disproportionately affect students with weaker undergraduate science backgrounds and those from underrepresented groups including English Language Learners and first-generation college students. Inclusive teaching practices aim to create a level field by removing barriers and providing equal access to students regardless of their background.It is hypothesized that technical flaws in MCQs increase their difficulty. The objectives of this study are: 1) to rate the quality of the MCQs used in a Dental Physiology course at Boston University and 2) to examine the effect of questions with technical flaws on item performance. To measure the performance of specific items, two analyses will be conducted: item difficulty, defined as the percentage of students who choose an item correctly, and item discrimination which refers to the correlation of how well a test taker does on a particular item and their performance on the whole test.An evaluation instrument based on the one developed and validated by Breakall et al. (2019) was employed to identify item writing flaws that add irrelevant difficulty. Examples of item flaws that provide irrelevant difficulty based on the National Board of Medical Examiners (NBME) guidelines are: (a) items with complicated stems and lead-ins that include negative forms, (b) item options that are not written succinctly or include vague terms, (c) numerical data not presented consistently, (d) items that include nonparallel options, or (e) that include “none of the above.” This instrument was used to assess MCQs from a Dental School Physiology exam.The frequency of item flaws indicated that of all items analyzed, 56% items contained at least one flaw. The most common item flaws identified were those where the answer choices were not of approximately the same length (32%), did not have parallel grammatical form and structure (24%) or those that included negative phrasing (16%). In conclusion, this assessment indicates that the MCQs used in this Dental Physiology course have room for improvement. To better understand if the identified flaws affect item performance, exam data provided by Exam Soft Analytics will be analyzed. Based on those results, decisions could be made about modifying MCQs to better serve the needs of our diverse student population. References: Breakall, J., Randles, C., & Tasker, R. (2019). Development and use of a multiple-choice item writing flaws evaluation instrument in the context of general chemistry. Chem. Educ. Res. Pract. 20(369), 369-382. This is the full abstract presented at the Americ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"29 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80125272","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":"The potential role of matrix metalloproteinases on reducing small artery stiffness and improving vasodilation in old spontaneously hypertensive rats","authors":"Marc A. Augenreich, T. Jurrissen, Francisco I. Ramirez-Perez, Jorge A. Castorena‐Gonzalez, Mariana Morales‐Quinones, Christopher A. Foote, Z. Nourian, O. Lateef, Luke Sun, Michael Hill, G. Meininger, J. Padilla, L. Martinez‐Lemus","doi":"10.1152/physiol.2023.38.s1.5791195","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5791195","url":null,"abstract":"Arterial stiffening is a major risk factor for cardiovascular disease development and progression. Both hypertension and aging are associated with presence of microcirculation endothelial dysfunction, hypercontractility, and vascular stiffening. Reports suggest that while hypertension results in inward remodeling, aging is associated with either no changes in internal diameter or outward remodeling with or without increases in wall thickness. Herein, we hypothesized that small arteries from old spontaneously hypertensive rats (SHR) would be inwardly remodeled and stiffer than old normotensive Wistar Kyoto (WKY) rats due to aggravated endothelial dysfunction, hypercontractility, and an increased presence of vascular smooth muscle stress fibers and collagen to elastin ratios. We further hypothesized that these characteristics would be associated with reduced expression of matrix metalloproteinases (MMPs). These hypotheses were tested in mesenteric arteries isolated from 88-week-old SHR and WKY rats. All reported differences are significant at P<0.05. SHRs had increased mean arterial pressure (P), pulse P, and heart weight normalized to body weight vs WKY rats. No differences in small mesenteric artery responses to phenylephrine or acetylcholine were observed between the rat strains. However, responses to the sodium nitroprusside were greater in SHR than in WKY isolated arteries. SHR arteries also had increased wall thickness and wall to lumen ratios, in addition to reduced cross-sectional compliance at 5-40 mmHg intraluminal P and lesser incremental modulus of elasticity at 80-120 mmHg. No differences in content of the extracellular matrices, collagen or elastin, were observed between arteries from either strain, whereas smooth muscle F-actin stress fibers were more abundant in the SHR arteries and MMP-2 and -9 expression were increased in the SHR arteries. In conclusion, these data suggest the interaction of age and hypertension in SHRs is associated with hypertrophic remodeling and increased responsiveness to nitric oxide likely due to increased MMP activity and reduced arterial stiffness. NIH HL-088105-02 to LAM-L This is the full abstract presented at the American Physiology Summit 2023 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":"37 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80176915","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":"PTSD induced inflammation negatively impacts cardiac homeostasis","authors":"A. Corker, Miguel Troncoso, Philip Broughton, Sara J. Sidles, R. Kelly, A. LaRue, K. DeLeon-Pennell","doi":"10.1152/physiol.2023.38.s1.5733437","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5733437","url":null,"abstract":"Multiple studies indicate that post-traumatic stress disorder (PTSD) is a risk factor for cardiovascular disease (CVD), however the mechanisms behind this correlation is unknown. We hypothesize that PTSD stimulates recruitment of monocyte-derived macrophages to the heart, resulting in increased cardiac fibrosis and resetting cardiac homeostasis. To induce experimental PTSD, male C57BL/6 mice were given 5 different foot-shocks (IFS; 1.0 mA, 1 sec duration) in 6 min. Before each shock, a tone was played to act as the PTSD-associated trigger. Control mice were also placed in the IFS chambers for 6 min but did not receive foot shocks. Behavioral testing was performed to characterize mice into non-responders (NR; IFS mice that do not demonstrate PTSD-like behavioral characteristics) and PTSD-like mice. Terminal timepoints selected were 4-weeks (4.6±0.7 months old) and 13-weeks (8.2±0.0 months old) post-IFS. Doppler echocardiography was collected at the 4-week time point. Histological and immunoblot assessments were collected at 13-weeks post-IFS to determine chronic alterations in cardiac homeostasis. Doppler measurements revealed that 4-weeks post-IFS, PTSD-like mice had decreased aortic ejection time (p<0.05) and trended toward increased isovolumetric relaxation (p=0.080) and contraction (p=0.088) time compared to controls. Interestingly at 13-weeks post-IFS, cardiomyocyte size was also elevated in PTSD-like mice compared to controls (p<0.05), suggesting the functional changes observed at 4-weeks reflect elevations in myocardial stress. A decrease in spleen weight at 4- (p<0.05) but not at 13-weeks (p=0.30) post-IFS indicate potential recruitment of immune cells acutely in PTSD-like mice. In line with spleen weights, at 4- and 13-weeks post-IFS, macrophage staining showed elevated levels in the LV of PTSD-like mice but not NR compared to controls (p<0.05 for all). In addition, matrix metalloproteinase (MMP)-9 protein levels were increased in the LV of PTSD-like mice compared to controls 13-weeks post-IFS (p<0.05). Collagen volume fraction was elevated at 13-weeks post-IFS in PTSD-like and NR mice compared to controls (p<0.05 for all). Our data indicates PTSD-induced cardiac stress is leading to macrophage recruitment and cardiac fibrosis which likely over time will lead to deterioration of myocardial function. This work was supported by the National Institutes of Health T32GM123055; the American Heart Association Innovator Project IPA35260039; the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award IK2BX003922; and South Carolina Translational Research Center UL1TR001450 This is the full abstract presented at the American Physiology Summit 2023 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":"67 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80248405","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":"The dependence of maximum oxygen uptake on hemoglobin-oxygen affinity and altitude: a computational modeling approach","authors":"Kevin L. Webb, C. Wiggins, T. Secomb, M. Joyner, T. Roy","doi":"10.1152/physiol.2023.38.s1.5716173","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5716173","url":null,"abstract":"Background: Hemoglobin, the primary oxygen-carrying protein in humans, provides the intermediate link between pulmonary oxygen uptake and tissue oxygen consumption. Oxygen transport is greatly influenced by the hemoglobin-oxygen affinity, which is commonly characterized by the metric P50 - defined as the oxygen tension at which 50% of hemoglobin is saturated. Humans with rare hemoglobin mutations causing a low P50 (high hemoglobin-oxygen affinity) have demonstrated remarkable preservation of exercise tolerance at high altitude conditions (~3,000m). However, the influence of a low P50 on V̇O2max at extreme altitudes (&gt;5,500m) remains largely unexamined. To examine the dependence of V̇O2max on P50 and altitude, we developed a computational model of oxygen uptake and utilization. We hypothesized that a low P50 would result in a better maintained V̇O2max at extreme altitudes compared to conditions of normal P50 and high P50 (low hemoglobin-oxygen affinity). Methods: We created a model that couples pulmonary oxygen uptake with systemic oxygen utilization to estimate V̇O2max as a function of P50, hemoglobin concentration, and altitude. Fixed values for cardiac output and tissue oxygen demand for V̇O2max at sea level were assigned in accordance with experimental data. The pulmonary oxygen uptake model assumes a single blood compartment exposed to alveolar gas, from which the arterial oxygen tension may be estimated from venous input. Using the alveolar gas equation, we interpolated respiratory parameters from data obtained during human sojourn to the summit of Everest. The systemic oxygen utilization model uses arterial input parameters along with Michaelis-Menten kinetics to compute oxygen consumption. The Fick principle was used to determine the venous oxygen tension, which was assumed to approximate tissue oxygen tension. From these values, systemic oxygen extraction and V̇O2max were determined as a function of P50, hemoglobin concentration, and altitude. Results: We present the results for several cases of P50 (low, normal, and high) and hemoglobin concentrations as a function of altitude. For a low P50, the model demonstrated a greater arterial oxygen saturation, greater oxygen content, and lower systemic extraction at extreme altitudes compared to values determined for cases of normal and high P50. Additionally, a low P50 led to better maintenance of V̇O2max at ~8,850m (~38% decrease from sea-level V̇O2max) compared to values determined for normal P50 and high P50 (~53% and ~67% decrease from sea-level V̇O2max, respectively, P&lt;0.05). Conclusion: This model demonstrates the importance of P50 in the determination of V̇O2max at various altitudes. At low altitudes, a low P50 does not confer an advantage in terms of oxygen utilization, likely due to diffusive oxygen limitations. However, at high and extreme altitudes, a greater convective oxygen transport associated with a low P50 likely outweighs impairments in oxygen diffusivity. This project was sup","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"41 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80327588","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":"Sex difference in the activation of central autonomic control regions in chronic intermittent hypoxia","authors":"Cephas Appiah, J. Little, Steve Mabry, R. Cunningham, J. Cunningham","doi":"10.1152/physiol.2023.38.s1.5731691","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5731691","url":null,"abstract":"Obstructive sleep apnea (OSA) results in sustained daytime hypertension. Chronic intermittent hypoxia (CIH) mimics the repetitive bouts of arterial hypoxemia associated with OSA. Male Sprague Dawley rats treated with CIH develop sustained hypertension and increased activation of central autonomic regions that regulate mean arterial pressure (MAP). However, gonadally intact female rats exposed to modest CIH treatment are not hypertensive. In male rats, lesions of the median preoptic nucleus (MnPO) prevent CIH-induced increase of MAP. We hypothesize that activation of MnPO and other autonomic control regions may contribute to the sex differences in the MAP response to CIH. To test this hypothesis, adult gonadally intact male and female rats (250-300 g bw) were exposed to either continuously normoxic (CON) or treated with CIH (10% O2 every 3 mins alternating with 21% O2 every 3 mins, 8 h/day) for 7 days. One week before the experiment started, some rats were instrumented with radiotelemetry transmitters to measure MAP and heart rate (HR). After one week of baseline recording, the rats were exposed to either normoxia or CIH and were euthanized (inactin 100 mg/kg ip) on the 8th day for immunohistochemistry. Forebrain and brainstem sections were stained for FosB/ΔFosB. Forebrain sections were also stained for neuronal nitric oxide synthase (NOS1) while brainstem sections were processed for dopamine-β-hydroxylase (DBH). The numbers of cells positive for NOS1 and FosB neurons in MnPO were counted and DBH and FosB positive neurons were counted in the hindbrain autonomic regions. CIH was associated with increased FosB staining in males but not females. Male exhibited an increase in the average number of FosB positive neurons (CON male 20 ± 2 cells/section, CIH male 35 ± 3; CON female 11 ± 1, CIH female 12 ± 2,) and colocalization of FosB and NOS1 (CON male 10 ± 1 cells/section, CIH male 18 ± 4; CON female 5 ± 1, CIH female 6 ± 1) in the MnPO. CIH females (n = 3) did not demonstrate increases in the numbers of FosB positive cells or DBH positive neurons in the commissural nucleus tractus solitarius (CON 7 ± 2, CIH 8 ± 2), rostral ventrolateral medulla (CON 2 ± 1, CIH 3 ± 1), caudal ventrolateral medulla (CON 5 ± 1, CIH 6 ± 2), and area postrema (CON 2 ± 1, CIH 2 ± 1) compared to CON females (n = 2). These preliminary results suggests that CIH is associated with increased FosB staining in the autonomic regions of male rats as opposed to female rats which is consistent with our working hypothesis. In addition, CIH was associated with increased FosB staining in NOS1 positive MnPO neurons suggesting that they may play a role in the sustained hypertension reported in male rats. The research is funded by NIH grant RO1 HL155977 This is the full abstract presented at the American Physiology Summit 2023 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 ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"53 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80424965","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":"Brachial artery flow-mediated dilation during incremental handgrip exercise is not impacted by sex or female sex hormones","authors":"Meghan Annis, Andrew W D'Souza, Geoff B Coombs, Kazumasa Manabe, Belinda Sanchez, Qi Fu, K. Shoemaker","doi":"10.1152/physiol.2023.38.s1.5731551","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5731551","url":null,"abstract":"Sex differences exist in reactive hyperemia flow-mediated dilation (RH-FMD), with males demonstrating larger RH-FMD responses than naturally menstruating females and females using oral contraception (OC). This difference is thought to be partly attributed to sex hormones. Among females, some studies demonstrate lower RH-FMD in females using OC relative to naturally menstruating females. To date, non-invasive assessments of endothelial function in males, naturally cycling females and females using OC have only been completed using RH-FMD. Notably, due to differences in the shear stimulus during sustained shear-induced FMD (SS-FMD) versus the transient pattern observed with RH-FMD, SS-FMD may provide distinct insight into endothelial dysfunction undetected with RH-FMD. Therefore, we hypothesized that the SS-FMD responses to incremental handgrip (IHG) exercise would be greatest in males, and that females using OC would have the smallest increase in SS-FMD compared to males and naturally menstruating females. The IHG protocol consisted of 3-minute stages of rhythmic handgrip exercise at 15, 30, and 45% of an individual’s maximal voluntary contraction (MVC) force, with no rest period between MVC transitions. Brachial artery diameter and blood velocity were measured simultaneously via duplex Doppler ultrasound in 10 males (26±4 [mean±SD] years), 11 naturally menstruating females (25±4 years), and 9 females using OC (27±5 years) during IHG. Females were tested in the mid-luteal (ML) and active (high hormone) OC phases. SS-FMD and shear rate were analyzed using linear mixed model analyses. MVC was greater in males relative to both groups of females (males: 40±6, ML: 28±8, OC: 26±6 kg; One-way ANOVA: post-hocs P≤0.001). Brachial artery shear rate was not different between males, ML females or females using OC throughout exercise (group-by-stage interaction: P=0.975). Consequently, the brachial artery dilated by 1.3±1.5, 0.1±2.1, and 1.2±3.6 % at 15% MVC, 4.0±3.1, 2.7±3.3, and 4.1±4.8 % at 30% MVC, and 9.1±4.9, 7.3±5.4, and 7.6±5.9 % at 45% MVC, in males, ML females, and females using OC, respectively (all P>0.05). Furthermore, the slopes of the relationship between the change in brachial artery diameter and shear rate was similar between the three groups (Males: 0.0004±0.0002, ML: 0.0003±0.0002, OC: 0.0003±0.0002 Δmm/Δ1·s-1; One-way ANOVA: P=0.564). Taken together, these data indicate that endothelial function in response to sustained elevations in shear stress are not impacted by biological sex or OC use. Supported by the Natural Sciences and Engineering Research Council of Canada, and IEEM indirect funds. This is the full abstract presented at the American Physiology Summit 2023 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":"73 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80449291","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":"Allelic modulation of mesenteric artery mechanical properties in young and adult APOE3 and APOE4 mice","authors":"Jana Frantz, K. Wagner, Jazmin N. Dunlap, Nikhil Sharma, Khalil Pathan, Jason Gallo, Brikena Gusek, Carleton Jones, D. Eckman","doi":"10.1152/physiol.2023.38.s1.5735180","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5735180","url":null,"abstract":"Previous studies from our lab have demonstrated age-related changes in vascular structure/function in posterior cerebral arteries (PCA) and left common carotid artery (CA) in male and female mice expressing human-ApoE targeted replacement of APOE3 (B6.129P2-Apoetm2(APOE*3)MaeN8) and APOE4 (B6.129P2-Apoetm3(APOE*4)Mae N8) (Taconic Labs). Therefore, we hypothesized that similar changes may be observed in the peripheral circulation. We isolated 3rd-order mesenteric arteries (MA) from young (Y, 3 to 4 mo) and adult (A, 7 to 10 mo), male and female mice expressing hPOE3 and hAPOE4. Mesenteric artery segments (5-8 mm in length) were isolated and cannulated on an arteriograph to assess vascular mechanical properties (lumen diameter (LD), wall thickness (WT), wall cross-sectional area (CSA), wall:lumen ratio (WL), distensibility (Dist), and stress/strain (SvS) under passive conditions (Ca2+-free Krebs + diltiazem) at intraluminal pressures ranging from 10-140 mmHg. Data were analyzed using two-way ANOVA, Student’s t-test, and analysis of nonlinear fit. Values were considered statistically different at P<0.05. Our data indicate that LD was greater in YE4 compared to YE3 mice (P<0.05), but was smaller in AE4 compared to AE3 mice (P<0.05). WT and WL was greater in YE3 mice compared to YE4 mice (P<0.05), but greater in AE4 compared to AE3 mice (P<0.05). While Dist was similar between YE3 and YE4 mice, AE4 mice exhibited less Dist than AE3 mice (P<0.05). Interestingly, distensibility increased between YE3 and AE3 mice (P<0.05), but was not significantly different between YE4 and AE4 mice. While compliance was similar between YE3 and YE4 mice, and similar between AE3 and AE4 mice, AE4 mice displayed decreased compliance compared to YE4 mice. No difference was seen between YE3 and AE3 mice. Wall stress was greater in YE4 mice compared to YE3 mice, but smaller in AE4 mice compared to AE3 mice (P<0.05), and an analogous pattern was observed in Einc for young and adult mice (P<0.05). These data indicate contrasting patterns of age-related vascular changes between allelotypes. Furthermore, these preliminary findings suggest that MA from A E4 mice exhibit a trend toward a hypertensive phenotype. Support: ABRC/ADHS18-205211 (DME, CBJ), Arizona Alzheimer's Consortium (funded by the Arizona Department of Health Services, Contract No. CTR040636) and matching funds from Midwestern University (DME), Biomedical Sciences Program (JF, KW, JD, DME), Biomedical Sciences Start-up Funds (DME) This is the full abstract presented at the American Physiology Summit 2023 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":"14 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78897842","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}