bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II induces endothelial dysfunction by downregulating TRPV4 channels
Authors: KONDAPALLI NARENDRA BABU , Katari Venkatesh , Dalal Kesha , Paruchuri Sailaja , Thodeti Charles 
Published: May 2023

Angiotensin II (Ang II) is a potent vasoconstrictor of vascular smooth muscle cells and implicated in hypertension, but it’s role in the regulation of endothelial function is not well known. We and others have previously shown that mechanosensitive ion channel, TRPV4 mediates flow- and/or receptor-dependent vasodilation via nitric oxide (NO) production in endothelial cells. Ang II was demonstrated to crosstalk with TRPV4 via AT1R and beta-arresting signaling in epithelial and immortalized cells, however, the role of this crosstalk in endothelial cell function is unexplored. Here, we demonstrate that pre-treatment with Ang II (200 nM for 48 h) significantly abolished TRPV4 mediated calcium influx in human microvascular endothelial cells, HMEC-1 (human EC). Further, Ang II treatment significantly downregulated TRPV4 protein expression in human EC without altering TRPV4 mRNA levels. Furthermore, Ang II-treatment significantly inhibited TRPV4-induced eNOS phosphorylation in human EC. Taken together, these results suggest that Ang II, in addition to eliciting smooth muscle contraction, contributes to hypertension by reducing TRPV4 protein expression and dependent NO production in human EC. This work is supported by NIH (1RO1HL119705, 1R15CA202847-01 and R01 HL148585), AHA Grant in Aid (14GRNT20380935, AHA- TPA-971237) and start-up funds from University of Toledo (CKT). 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.
Arterial and Intracranial Hypotension During and Following Exercise
Authors: Petersen Lonnie 
Published: May 2023

Exercise induced arterial hypertension and post-exercise arterial hypotension (PEH) are well-described phenomena with direct impact on cerebral blood flow. Cerebral perfusion pressure is given by the difference between mean arterial pressure at brain-level (MAPbrain) and intracranial pressure (ICP), however, little is known about effects of moderate aerobic exercise on ICP. We hypothesize that moderate exercise does not increase ICP thereby facilitating the augmented cerebral blood flow and that a post-exercise decrease in ICP is a contributing mechanism to maintained cerebral blood flow during PEH.Non-invasive (N=14) and invasive (N=3) ICP recordings and cardiovascular parameters were measured upright and supine before, during, and after 30 minutes of seated moderate aerobic bicycle exercise. Exercise elevated MAPbrain from 68±4 to 82±7 mmHg (mean±SEM, P<0.05) without elevating ICP, thus increasing CPP (72±3 to 87±6 mmHg, P<0.05). Compared to before exercise, we found significant PEH with a decrease in MAPbrain of 5±3% (5 mmHg; P<0.05), predominantly driven by a 26±5% (P<0.0001) decrease in total peripheral resistance (TPR). Because post-exercise ICP decreased concomitantly by 58±20% (P<0.0001) CPP remained unchanged. Recovery of ICP towards baseline was similarly correlated to TPR-recovery (R2=0.92, P<0.001), all variables returned to baseline within one hour.Here, we show for the first time ICP during and following aerobic exercise and consequences for cerebral perfusion. Periodic PEH is cardio-vascular protective and has long-term benefits for hypertensive patients, here we suggest that post-exercise decreases in ICP could similarly be cerebo-protective and in part explain the long-term beneficial effects of exercise for cerebral health and cognition. This work was supported by NASA grant no 80NSSC19K0020 and the Novo Nordic Foundation grant no NNF15OC0019196 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.
Leptin is a key regulator of glucose homeostasis in obesity
Authors: Simonds Stephanie , Pryor Jack , Cowley Michael 
Published: May 2023

Approximately 9 out of 10 people with type-2 diabetes are overweight. Leptin is a hormone secreted from white fat cells that exerts control over both food intake and energy expenditure. We described the central mechanisms underlying the hypertensive effects of hyperleptinemia in obesity. Work presented here used continuous radiotelemetric glucose monitoring in mice in combination with multiple gold standard techniques in order to determine the effects of dorsomedial hypothalamic (DMH) leptin signalling on peripheral glucose control. A leptin receptor (LepR) antagonist administered directly into the brain impaired DIO mouse glucose tolerance demonstrating that leptin retains the ability to regulate blood glucose concentration in obesity. Knockdown of DMH LepR function using short hairpin adeno-associated virus (AAV) RNA significantly reduced brown adipose tissue (BAT) thermogenesis by -0.8 ± 0.1°C and increased basal blood glucose (14.3 ± 0.6mmol/l to 9.4 ± 0.5mmol/l) and impaired glucose tolerance. Conversely, chemogenic activation of LepR-expressing DMH neurons significantly elevated BAT thermogenesis (1.5 ± 0.2 °C increase). This increased BAT temperature was immediately followed by a decrease in plasma blood glucose concentration (7.6 ± 0.5 mmol/l to 5.8 ± 0.5 mmol/l). Work presented here demonstrates that increasing the activity of LepR expressing neurons in the DMH can improve glucose tolerance in obesity though an elevation of BAT metabolic activity. This work was supported by the National Heart Foundation of Australia (SES), The National Health and Medical Research Council of Australia (SES and MAC). 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.
Sex Differences in Heart Rate Variability during Metaboreflex Activation
Authors: Pereira Tania , Edgell Heather 
Published: May 2023

Women have been shown to experience blunted metaboreflex activation compared to men (Jarvis et al., 2011; Joshi & Edgell, 2019; Minahan et al., 2018; Samora et al., 2020), which may derive from altered autonomic balance. Since heart rate variability (HRV) estimates sympathetic and parasympathetic outflow, this study aims to determine if there are sex differences in HRV during metaboreflex activation. High frequency (HF) power and greater RR interval variability (SDRR) represent cardiac parasympathetic outflow, whereas the ratio between low frequency (LF) and HF power (LF/HF) represents cardiac sympathetic outflow. Thirty-two young, healthy men (n=16) and women (n=16) were recruited to perform 2mins of isometric handgrip at 40% of their maximal voluntary contraction followed by 3mins of post-exercise circulatory occlusion (PECO). ECG was continuously recorded, and HRV analysis was determined using 3mins of ECG at baseline or PECO. In response to PECO, heart rate (Women 71±12bpm vs. 73±13bpm; Men 68±12bpm vs. 72±13bpm; p=0.026) and mean arterial pressure (Women 84±8mmHg vs. 93±10mmHg; Men 85±9mmHg vs. 97±11mmHg; p<0.001) increased equally in both sexes. There were no significant differences in SDRR, root mean square standard deviation, and total power due to sex or PECO (all p>0.07). At all timepoints and compared to men, women had 1) significantly lower LF power (Women 19±10nu vs. 24±16nu; Men 42±21nu vs. 49±17nu; p<0.001), 2) higher HF power (Women 78±9nu vs. 74±16nu; Men 57±20nu vs. 50±17nu; p<0.001), 3) higher proportion of RR intervals differences greater than 50ms (Women 60±21% vs. 58±22%; Men 39±16% vs. 35±20%; p=0.003), regardless of time (p>0.2), and 4) lower LF/HF (Women 0.26±0.17 vs. 0.41±0.42; Men 1.01±0.90 vs. 1.34±1.30; p=0.002). Unlike previous findings, no sex differences were observed in the pressor response to metaboreflex activation. HRV did not differ in response to PECO in both sexes; however, women had greater cardiac parasympathetic dominance than men. Funding provided by Natural Sciences and Engineering Research Council of Canada 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.
Corncob bedding alters fasting blood glucose and vascular function in mice
Authors: Sveeggen Timothy , Isakson Brant , Straub Adam , Bagher Pooneh 
Published: May 2023

Rodent husbandry requires careful consideration of environmental factors that may impact colony performance and subsequent physiological studies. Of note, recent reports have suggested corncob bedding is potentially a confounding variable affecting a broad range of organ systems. As corncob bedding may contain digestible hemicelluloses, trace sugars, and fiber, we hypothesized that corncob bedding impacts murine vascular function and overnight fasting blood glucose. Here, we compared mice housed on corncob bedding, which were then fasted overnight on either corncob or ALPHA-dri bedding, a paper cellulose alternative. Male and female mice were used from two non-induced, endothelial-specific conditional knock-out strains (Cadherin 5-CreERT2, floxed hemoglobin alpha 1 [Hba1] or Cadherin 5-CreERT2, floxed cytochrome B5 reductase 3 [CyB5R3]) on a C57BL/6J genetic background. After fasting overnight, initial blood glucose was measured, and mice were anesthetized with isoflurane for measurement of blood perfusion via laser speckle contrast analysis using a PeriMed PeriCam PSI NR system. After a 15-minute equilibration, the mice were injected intraperitoneally with phenylephrine (5 mg/kg) or saline and monitored for changes in blood perfusion. After a 15-minute response period, blood glucose was remeasured post-procedure. Consistently, mice fasted on corncob bedding had higher blood glucose than the ALPHA-dri group. In the CyB5R3 strain, corncob bedding caused a reduction in phenylephrine-mediated vasoconstriction. In the Hba1 strain, phenylephrine-induced vasoconstriction was more variable in the corncob group. Altogether, this work suggests that corncob bedding could be a confounding variable for vascular measurements and fasting blood glucose in mice. To promote scientific rigor and improve reproducibility, bedding type should be included in published methods. NIH R01HL155618 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.
Opioidergic Regulation of AgRP Neurons
Authors: Atasoy Deniz , Sayar Atasoy Nilufer , Yavuz Yavuz , Laule Connor , Dong Chunyang , Kim Hyojin , Aklan Iltan , Tian Lin 
Published: May 2023

Opioids are generally known to promote hedonic consumption. Although much of the existing evidence is primarily based on studies in mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits; however, their role in homeostatic feeding remains unclear. The objective of this study is to understand the role of mediobasal hypothalamic opioid signaling in appetite regulation. We hypothesize that opioids may act as negative regulators of appetite through suppression of hunger neurons. Here we used a novel fluorescent opioid sensor, deltaLight for in vivo imaging of opioid dynamics along with ex vivo electrophysiology to study opioid's impact on appetite neurons. We report that mediobasal hypothalamic opioid levels rapidly increase by feeding, which, in turn, directly inhibit AgRP neurons through mu-opioid receptor (MOR). AgRP specific MOR expression increases by energy surfeit and contributes to opioid induced suppression of appetite. Conversely, its antagonists diminish suppression of AgRP neuron activity by food and satiety hormones. Mice with AgRP neuron specific ablation of MOR expression increased preference for palatable food consumption when given the choice. These results define AgRP neuron specific MOR signaling as a key mediator of diet choice thorough post-ingestive signals. 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.
Chronic hypoxia disrupts memory T regulatory cell phenotype which contributes to the pathogenesis of pulmonary hypertension
Authors: Lantz Benjamin , Moriwaki Mika , Oyebamiji Olufunmilola , Guo Yan , Garcia Selina , Gonzalez Bosc Laura 
Published: May 2023

Pulmonary hypertension (PH) caused by chronic hypoxia (CH) is a multifaceted disease most often caused by sleep apnea, prolonged high-altitude exposure, or chronic obstructive pulmonary disease (COPD), with minimal treatment options, leading to right heart failure and death. One major contributor in the pathogenesis of PH that requires more characterization is the accompanying immune response.Our previous studies have demonstrated the importance of inflammation and self-immunity in CH-induced PH. We demonstrated pulmonary-perivascular localization of pro-inflammatory Th17 cells as well as an increase in total Th17 cells in the lung, while finding no overall changes in the number of anti-inflammatory T regulatory (Treg) cells present in the lung. Imbalance between Th17 and Treg cells has been shown to drive multiple inflammatory and metabolic diseases. One area of interest related to this balance has been the recent discovery and attempted characterization of exTregs, or cells that, at one point in time, were Tregs but lost their phenotype transitioning to pro-inflammatory Th17 cells, due to decreases in the expression of the transcription factor FoxP3. Therefore, we hypothesized that the increase in Th17 cells seen in CH is due to a decrease in Tregs and Treg suppressive capacity as well as a switching of Tregs to Th17 cells. Using a mouse model that allows the study of lineage stability and genetic mapping of Tregs, together with single-cell RNA sequencing (scRNA SEQ), we initially established that CH resulted in a gene expression profile consistent with exTregs or Tregs with less suppressive activity, such as downregulation of Il2ra gene and upregulation of Tnfrsf4 (adjusted p-value 0.03). To further establish a loss in Tregs as well as an increase in exTregs following CH exposure, we performed spectral flow cytometry of splenocytes on a Cytek Aurora to look for changes in protein expression and cell prevalence. Finally, we used a similar lineage mapping mouse model to look at Th17 cells. Following these experiments, we found supporting evidence of our scRNA SEQ data, finding a decrease in Tregs in both male and female mice following CH exposure, as well as an increase in exTregs in both groups exposed to CH. We also further supported this data finding Th17 cells tracked through our model to be increased following CH. These results support the importance of immune cell balance and inflammation in the pathogenesis of CH-induced PH. R56 HL153065-01 NIH, AHA 18TPA34170037, AHA967925 & T32 HL07736 NIH 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.
Cardiomyocyte-specific overexpression of Larp6 protects against angiotensin II-induced cardiac dysfunction
Authors: Russell Jacob , Yoshida Tadashi , Ma Lixin , Davis Daniel , Grisanti Laurel , Russell Adam , Ruff Margot , Bailey Chastidy , Bender Shawn , Chandrasekar Bysani 
Published: May 2023

Introduction: La ribonucleoprotein 6 (Larp6) is a multifunctional mRNA binding protein that interacts with type I collagen mRNA to increase its half-life, translation, and deposition. However, its role in the heart is not known. To investigate the role of Larp6 in cardiac function and remodeling, we generated a cardiomyocyte-specific Larp6 overexpressing (OE) transgenic mouse model (Larp6-Tg), and investigated its role at (i) baseline and (ii) following hypertensive challenge with angiotensin II (Ang II). We hypothesized that Larp6 OE exacerbates Ang II-induced cardiac remodeling and dysfunction. Methods: Cross-sectional studies were performed from 2-8 months of age in male and female Larp6-Tg and wild-type (WT) littermates. Baseline cardiac function was assessed by 7-T MRI and echocardiography. In another set of mice, hypertension was induced by infusion of Ang II by osmotic minipump (1000 ng/kg/min) and compared to vehicle infusion. Blood pressure (BP) was assessed 14-17 days post-surgery via tail-cuff, cardiac function by echocardiography after 21 days, and a mid-section of heart was fixed for histochemistry. Results: Baseline cross-sectional studies revealed that Larp6 OE had no significant effect on cardiac function (7-T MRI), BP, or gross morphology regardless of sex. At 10 months of age, histochemistry revealed increased cardiomyocyte Larp6 protein expression and fibrosis in Larp6 OE mice. In 10-month-old mice, Ang II infusion increased BP and induced cardiac hypertrophy in both male and female Larp6-Tg and WT mice. Ang II induced systolic dysfunction in WT mice, however Larp6 OE significantly protected against Ang II-induced decreases in ejection fraction, fractional shortening, and cardiac output independent of sex. These data provide insight into novel roles of Larp6 in the heart worth further examination. Conclusions: Transgenic overexpression of Larp6 in cardiomyocytes doesn’t affect basal cardiac function. However, under hypertensive conditions, its overexpression protects against systolic dysfunction independent of sex. These unanticipated protective effects of Larp6 will be further evaluated through histology and transcriptomics to understand the underlying molecular mechanisms of protection. Together, our data show for the first time that induction of Larp6 has potential to blunt the progression of hypertensive heart disease. Funding: NHLBI R01 HL088105, R01 HL136386, R01 HL142770, NIDDK DK130243, SRCS (IK6BX004016), and merit BX005845. 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.
Evaluation and Implementation of Lifestyle Habits and Life's Simple 7 in Northwest Indiana
Authors: Thivierge Grant , Ladwig Matthew , Mutai Ezra , Bishop Reagan , Durocher John 
Published: May 2023

The CDC’s Social Vulnerability Index (SVI) provides insight into many factors that contribute to the lack of health equity, such as poverty, lack of transportation, and crowded housing. Purdue University Northwest (PNW) has campuses located in Hammond, IN (Lake County) and in Westville, IN (LaPorte County). Because of the high SVI near the Hammond (i.e., 0.9615) and Westville (i.e., 0.8816) campuses, PNW is uniquely positioned to help address the health issues and challenges associated with high SVI. The purpose of this ongoing project is to evaluate and implement lifestyle changes suggested by the American Heart Association’s Life’s Simple 7™ in at least 60 local residents. To accomplish this goal, the PNW Integrative Physiology and Health Sciences (IPHS) Center offers free seminars on each of the Life’s Simple 7™ topics as well as free health screenings to reduce barriers to preventive care among students and community members. To-date, 48 (21 male; 27 female) unique individuals have attended a seminar and / or utilized the free health screening services. The seminar topics include, 1) How to Manage Blood Pressure, 2) How to Control Cholesterol, 3) How to Eat Better, 4) How to Stop Smoking, 5) How to Manage Weight, 6) How to Be More Active, and 7) How to Reduce Blood Sugar. Students and community members that attend lectures in person or virtually also receive take-home educational materials related to improving and maintaining cardiovascular health as well as giveaways including blood pressure monitors, pulse oximeters, pedometers, resistance band kits, and at-home A1C testing kits. The health screenings include blood pressure, body composition, cholesterol, blood sugar, triglycerides, and hemoglobin A1C, as well as healthy eating information, dietary surveys, and physical activity surveys. This project will continue through June 30, 2023. The Indiana Department of Health (Health Issues and Challenges Grant) 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.
The Effects of Mindfulness-Based Stress Reduction and Stress Management Education on Arterial Stiffness, Trait Anxiety, and Sympathetic Regulation
Authors: Thivierge Grant , Vyas Aditi , Morin Brigitte , Larson Robert , Durocher John 
Published: May 2023

Mindfulness-based stress reduction (MBSR) has been shown to reduce blood pressure and anxiety in several studies, but the effects of MBSR on arterial stiffness and muscle sympathetic nerve activity (MSNA) have not been studied. We hypothesized that MBSR would lower arterial stiffness and MSNA. The present study randomized 22 adults (17 male; 5 female; age 25±1 years; BMI 26±1 kg/m2) with elevated blood pressure (i.e., ≥120/80 mmHg) into 8 weeks of MBSR or stress management education (SME). We examined resting blood pressure, heart rate, trait anxiety, arterial stiffness, and MSNA within 10 days before and after each of the 8-week interventions. Ten participants were randomized into the MBSR group, and 12 into the SME group. Resting blood pressure and heart rate were recorded as the average of three readings from an automated cuff in the seated position. Arterial stiffness was estimated as the average of two carotid-femoral pulse wave velocity (cfPWV) recordings in the supine position, and MSNA was recorded as burst frequency via direct post-ganglionic recordings from the peroneal nerve in a subset of participants. Mean arterial blood pressure was unchanged from pre- to post in either group, but heart rate was reduced from pre- to post in the MBSR participants (77±4 vs. 69±3 beats/min; p=0.01). There was a significant time-effect for trait anxiety, with raw scores reduced from pre- to post (38±3 vs. 34±2 a.u.; p=0.02). cfPWV was unchanged from pre to post (5.6±0.2 vs. 5.4±0.2 m/s; p=0.25), and MSNA was also unchanged (time-effect p=0.51) by MBSR (14±2 vs. 12±3 bursts/min; n=5) or SME (16±1 vs. 15±2 bursts/min; n=5). Results of the present study confirm that MBSR can have beneficial effects such as reducing HR and trait anxiety. Our results suggest that MBSR and SME do not change arterial stiffness or resting MSNA, but this may deserve further investigation in other at-risk populations. NIH (1R15HL140596-01) 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.