bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension Reduces Aortic Strain in Both Sexes, but only Aorta from Female Rats Showed Increase in Stress: The Role of Appropriate Normalization Method to Evaluate Strain-Stress Parameters
Authors: Shiota Timmers Montandon Ian , Fontes Milene , Gebere Mengistu , Costa Tiago , Townsend Paul , Moura Kawane , Azhar Mohamad , Uline Mark , Webb Clinton , McCarthy Cameron , Wenceslau Camilla 
Published: May 2023

The gold standard of arterial stiffness measurements in isolated aorta is the stress-strain (SS) relationship. Wall thickness (WT) and artery inner diameter (ID) are variables that plot the SS curve and should be normalized to the dimensions of the individual subject. Previously, we used measurements from the current literature, but the data collected were not accurate. Therefore, we hypothesized that the measurements of the vascular structure using echocardiogram (ECHO) should be applied to evaluate tissue puller to obtain SS data. With that, we also hypothesized that aorta from spontaneously hypertensive rats (SHR) has greater stress and lower strain levels than normotensive Wistar rats. To test this hypothesis, thoracic aorta parameters from 3-month-old male Wistar (WM) (body weight: 449±6.87g, n=4), SHR male (SM) (body weight: 295±3.34g, n=4), Wistar Female (WF) (body weight: 250±8.50g, n=4), and SHR Female (SF 169.4±2.69g, n=4) rats were measured from an ECHO. After, animals were killed and aortas were cut in 2 mm segments and mounted on Tissue Puller to measure SS. The inner diameter (ID) and wall thickness (WT) were measured by the ECHO for all animals: [WM (WT: 0.519±0.014mm, ID: 2.042±0.11mm), SM (WT: 0.485±0.026mm, ID: 2.023±0.055mm), WF (WT: 0.504±0.01mm, ID: 1.628±0.092mm), SF (WT: 0.521±0.011mm, ID: 1.64±0.099mm)] and there were no significant difference between these values. We then normalized the SS curves to each of the arteries’ parameters for ECHO and we found there were significant decreases in the strain values in aorta from hypertensive rats, regardless of sex (WM: 1.775±0.108 vs SM: 1.370±0.058; p=0.0146), and (WF: 2.056±0.218 vs. SF: 1.713±0.224; p=0.0517). We found a trend in the stress from female rats (WF: 1367±61 mN/mm2 vs SF 2361±391 mN/mm2; p=0.0597). There were no differences between male rats (WM:1.269±153 mN/mm2 vs SM: 1319±80 mN/mm2; p=0.671).Overall, these data show that ECHO should be used to accurately measure rat aorta structural parameters under the tissue puller. They also show SHR and Wistar were different in both sexes in strain, but only female SHR vs Wistar showed differences in stress. National Institutes of Health - R00GM118885, R01HL149762, and R00HL151889. and McNair Junior Fellows (MJF) Program 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.
Targeting p21-highly-expressing Endothelial Senescent Cells Prevent Vascular Dysfunction Induced by High-Fat Diet
Authors: Kwon Oh Sung , Noh Sung Gi , Wang Lichao , Xu Ming 
Published: May 2023

BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular disease. Although high-fat diet shows increased vascular senescence and vascular dysfunction, it remains unclear how obesity could induce cellular senescence and whether vascular dysfunction is associated with senescence of cells in the vasculature. p21 is one of the major regulators and most recognized cellular markers for senescent cells. Recent evidence demonstrated that high fat diet induces the accumulation of p21 high cells in the endothelial cells. However, the relationship between p21 high cells and vascular function is not identified yet. Therefore, this study investigated the linkage between vasodilation and p21 high cells in aging or high-fat diet-induced vascular dysfunction. METHODS: Five p21-Cre/+; +/+ (P) and p21-Cre/+; DTA/+ (PD) obese mice fed by high fat diet were administrated with tamoxifen for twice. Five P lean mice fed by normal chow were adopted as normal control. We previously demonstrated that p21high cells accumulate in obese P mice, and can be eliminated in obese PD mice by tamoxifen treatment. Using pressure myography, vasodilation in femoral arteries was assessed in response to flow-induced shear stress, acetylcholine (ACh), and sodium nitroprusside (SNP). Free Radical Production were measured by Amplex Red Assays. One-way ANOVAs with Bonferroni post-hoc were used to determine differences between groups (P < 0.05). RESULTS: Endothelium-dependent vasodilation was significantly attenuated in the old, induced by both flow (Lean P: 62 ± 4, Obese P: 23 ± 3 %; p < 0.05) and ACh (Lean P: 77 ± 4, Obese P: 35 ± 4 %; p < 0.05). However, the clearance of p21 high cells using tamoxifen enhanced vasodilatory function response to both flow (Obese P: 23 ± 3 %, Obese PD: 58 ± 3 %; p < 0.05) and ACh (Obese P: 35 ± 4 %, Obese PD: 70 ± 3 %; p < 0.05) while endothelium-independent vasodilation was not altered by high fat diet. Also, high fat diet increased free radical production, but the clearance of p21 high cells using tamoxifen attenuated free radical production (Lean P: 10.16 ± 0.41 pmol·s-1·mg-1; Obese P: 26.83 ± 0.54 pmol·s-1·mg-1; Obese PD: 12.23 ± 0.54 pmol·s-1·mg-1; P<0.05). CONCLUSION: These results demonstrated that p21high cells may play a causal role in vascular dysfunction with obesity and other chronic disease. Therefore, targeting p21high cells may enhance vasodilatory function through decreasing oxidative stress. 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.
Tumor arteriolar function in a novel orthotopic model of breast cancer
Authors: Kunkel Olivia , Horn Andrew , Behnke Brad 
Published: May 2023

Introduction: For women in the United States, breast cancer is the most diagnosed non-skin cancer and second leading cause of cancer-related deaths. While the overall 5-year survival rate of all stages of breast cancer is 90%, several features of the tumor microenvironment contribute to an individual patient’s treatment success. The efficacy of radiation is dependent upon the presence of oxygen, and many solid tumors are hypoxic. In addition to its effect on treatment success, tumor hypoxia also leads to a more aggressive phenotype and increases metastatic potential. Therefore, improving tumor blood flow and thus, hypoxia, may improve the efficacy of radiation as well as reduce metastatic potential. The purpose of this study was to understand the vasomotor function of arterioles from orthotopic breast tumors to determine the potential mechanisms to improve tumor blood flow. Methods: Female Fischer 344 (retired breeder) rats were randomly assigned to non-tumor control (CON; n=4) and tumor bearing (TB; n=6) groups. TB rats were injected with 3x103 Mat B III cells into the mammary duct. Once tumors reached 10-15 mm in diameter, rats were euthanized and tumor feed arterioles were harvested. Blood vessels from CON rats were harvested from the mammary tissue. Vessels were cannulated on glass micro-pipettes, pressurized at 90 cmH2O, and allowed to equilibrate for one hour. Alpha (α)-adrenergic and myogenic contractile responses were assessed and vessel diameter recorded. Data were analyzed using a Two-Way Repeated Measures ANOVA and determined to be significant if p ≤ 0.05. Results: There were no differences between groups in α-adrenergic vasoconstriction or between active and passive pressure-diameter responses. There was no difference in maximal constriction to norepinephrine for CON vs. TB (53.07 ± 19.4% vs. 40.68 ± 13.9%) or maximal pressure-induced constriction (myogenic response) for CON vs. TB (11.2 ± 2.6% vs. 13.03 ± 5.0%). Conclusions: The vascular bed of rodent mammary tumors may be unique given that, unlike other solid tumor arterioles (i.e. prostate), breast tumor arterioles do not exhibit significant impairments in contractile response to norepinephrine or in myogenic vasoconstriction. Further investigation is needed to determine the vascular response to other stimuli (flow, bradykinin, etc.) and to quantify tumor hypoxia, but tumor blood flow may depend more heavily on vessel patency and vascular density than on the functional nature of the tumor vascular supply. Johnson Cancer Research Center 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.
Comparison of the EndoPAT device with a unique vascular assessment of reactive hyperemia
Authors: Ramraj Olivia , Badhwar Smriti , Edgell Heather 
Published: May 2023

The EndoPAT device (Itamar Medical) is used to determine endothelial function by using peripheral arterial tonometry during reactive hyperemia. It has been shown to be related to the gold standard non-invasive technique of flow-mediated dilation ultrasound assessment. These methodologies have technical requirements and/or ongoing operational costs that could be prohibitive to under-resourced clinics or researchers. We hypothesized that using a re-usable and cost-effective procedure of determining the reactive hyperemic response using piezo-electric pulse transducers (ADInstruments) would give similar results to the EndoPAT. Reactive hyperemia was induced by occluding blood flow to the forearm for 5 minutes using a blood pressure cuff inflated to +50mmHg above systolic blood pressure. The vascular response to the release of the occlusion was assessed using EndoPAT on the index fingers and using piezo-electric transducers on the middle fingers, concurrently. Twenty-five healthy participants (15 female; 31±12years) participated in the study. Participants refrained from caffeine, alcohol, fatty foods, smoking and strenuous exercise for at least 12 hours prior to testing. The EndoPAT reactive hyperemia index (RHI) was determined using proprietary software. The area under the curve (AUC) of the finger pulse waves from the piezoelectric pulse transducers was also determined. The ratio of the AUC of the peak hyperemic response (10s average) compared to the baseline period (3.5min) in the occluded arm was compared to the equivalent ratio in the control arm to determine the pulse-wave reactive hyperemia index (PWRHI). Univariate linear regression and correlation analysis was conducted between RHI and PWRHI. When comparing the two methods, Spearman’s r was 0.67 (p=0.0002) with a coefficient of determination of 0.58. We have found that the two methods correlate well to each other and the PWRHI technique has the potential to make microvascular assessments more accessible to clinicians and researchers. Our PWRHI method still needs to be validated in larger populations with vascular dysfunction and over a wider age-range. Funding provided by the 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.
Endothelial-Specific Expression of CIDEC Protects From Age-Induced Skeletal Muscle Capillary Rarefaction and Declined Muscle Performance
Authors: Balakrishnan Bijinu , Becker Chloe , Tenerowicz Kate , Puri Vishwajeet 
Published: May 2023

We recently found that Cell death-inducing DNA fragmentation factor-a–like effector C (CIDEC), originally identified as lipid droplet-associated protein in adipocytes, is abundantly expressed in endothelial cells. We described its novel role in regulating vascular function in humans. To study the effect of endothelial-specific CIDEC in whole-body physiology and its molecular action in regulating vascular function, we generated a humanized mice model expressing endothelial-specific human CIDEC transgene (E-CIDECtg). E-CIDECtg mice showed protection against HFD-induced glucose intolerance and dyslipidemia. We also identified a molecular pathway of action whereby CIDEC directly regulates the VEGFA-VEGFR2 axis promoting eNOS signaling, angiogenesis, and vasodilation to improve metabolic health. Since aging and age-related declines in physical activity are associated with physical and metabolic impairment, and skeletal muscle capillarization is reduced in older adults, the objective of the present study was to evaluate the role of endothelial-specific CIDEC in the regulation of microvasculature remodeling in muscle, as well as muscle performance with aging. One-year to 14 months old E-CIDECtg mice (around 60 yrs human age) and their littermate controls were tested for muscle endurance and capillary density in the skeletal muscle. E-CIDECtg mice displayed enhanced muscle performance and higher capillary density in the skeletal muscle. Serum lipid parameters, LDL, triglycerides, fatty acids, and total cholesterol were lower, and the metabolic parameters including respiratory exchange ratio (muscle’s oxidative capacity), insulin tolerance and glucose tolerance were higher in aged E-CIDECtg mice. Overall, our study highlights endothelial-specific role of CIDEC in improving age-related decline in capillary density, muscle performance, and metabolic health. R01HL140836 and funds from Osteopathic Heritage Foundation's Vision 2020 to Heritage College of Osteopathic Medicine at Ohio University 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.
Impacts of high altitude on cognitive function and hearing during acclimatization and after return to sea level
Authors: Nasr Ledia , Frost Shyleen , Kannan Lakshmi , Pham Kathy , Bazzani Lorenzo , Jacuinde Diego , Seitz Aaron , Heinrich Erica 
Published: May 2023

High-altitude exposure and associated acute hypoxemia have been shown to impact several cognitive function domains, including reaction times and sustained attention. However, questions remain regarding the mechanisms underlying these impairments. In this study, we aimed to determine if hyperventilation-induced hypocapnia played a role in these effects. Twenty healthy participants were recruited (n=13 men, 7 women) between the ages of 18 and 38 with no history of cardiovascular or pulmonary disease. Participants completed a 45-min cognitive function test battery once at sea-level (SL) in the laboratory (340 m elevation), 2-3 times at home prior to ascent, over three days at high-altitude (HA) (3800 m elevation), and 2-3 times at home after return to sea level (SL-R). During the lab and high-altitude sessions, participants were fitted with an oronasal facemask and were provided with room air (RA) or a mild hypercapnic gas mixture (sea-level equivalent of 4% inspired CO2) (HC) to stimulate increased cerebral blood flow. All participants received room air at sea-level. At high altitude, participants were divided evenly into RA or HC treatment groups in a participant-blinded randomized order. In a single-talker hearing task, hearing acuity was significantly reduced on the first 2 days at high altitude (p<0.001 for each) but returned to baseline levels by day 3 (SL: 28.7 ± 3.9 dB, HA1: 35.6 ± 3.4 dB, HA2: 36.5 ± 4.3 dB, HA3: 27.2 ± 5.2 dB). Hearing acuity also showed a trend for improvement in the RA group on the first day at high altitude compared to the HC group (RA: 34.3 ± 3.8 dB, HC: 37.1 ± 2.2 dB, p=0.070). Hearing acuity was also reduced following return to sea level (SL: 28.7 ± 3.9 dB, SL-R: 31.5 ± 5.7 dB, p=0.024). Total time spent on a trail making task showed a trend for an increase on the first day at high altitude (SL: 42.8 ± 6.6 sec, HA1: 46.5 ± 8.2 sec, p=0.062), but improved on the third day at high altitude (HA3: 33.3 ± 10.0 sec, p<0.001), with no impact of treatment on performance. Overall, this data supports previous work illustrating a mild impact of moderate high-altitude exposure (3800 m) on cognitive performance, which appear to improve with acclimatization. However, performance on these tasks was not improved with mild hypercapnia to increase cerebral blood flow. In addition, we provide new evidence of potential persistent impacts of high-altitude exposure on hearing after return to sea level. Support for this research was provided by a Chancellor's Research Fellowship to ECH, and a White Mountain Mini Grant to KP. 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.
Orexinergic signaling in the commissural nucleus of solitary tract participates in the hypercapnic ventilatory response during wakefulness in light phase of the diurnal cycle
Authors: Da Silva Eliandra , e Horta-Júnior José de Anchieta , Dias Mirela 
Published: May 2023

Despite of the unquestionable role of different body systems to acid-base balance, chemosensitive neurons distributed in different brain regions coordinate respiratory patterns to appropriately restore the PCO2 and thus, contributes to correction of variations in pH. Orexinergic (OX) neurons in the lateral hypothalamus/perifornical area acts on central chemosensitivity modulation in a vigilant state dependent manner, synchronized with the diurnal cycle and send projections to respiratory network in the brainstem. Considering that the commissural nucleus of NTS (NTSc) receives orexinergic projections and has notable participation in ventilatory responses to the increase of CO2 levels, our hypothesis is that orexin-A, acting on the orexin receptor-1 in the NTSc, influence the hypercapnic ventilatory response of rats across the diurnal cycle. To test this hypothesis, we measured the pulmonary ventilation (E) of unanesthetized male Wistar rats (250–320 g) in a whole-body plethysmograph system together with body temperature, EEG and EMG recordings during microdialysis of orexin receptor-1 antagonist (SB-334867; N-(2-metil-6-benzoxazolil)-N′-1,5-nafitridina-4-yl-ureia – 5 mM) into the NTSc. Experiments were performed in normocapnic and hypercapnic hyperoxic conditions (7% CO2 – 93% de O2) in the light and dark phase of diurnal cycle of the animals. All procedures were approved by Animal Care and Use Committee for the Institute of Biosciences at Botucatu – Brazil (CEUA – protocol nº. 6766090620). The results showed that microdialysis of the antagonist into NTSc caused a significant attenuation in CO2 ventilatory responses, compared with vehicle (aCSF), during wakefulness (VE= 1743 ± 224 mL kg-1min-1 versus VE= 2002 ± 232; n = 06; p < 0.05) but not during sleep (VE= 1793 ± 433 mL kg-1min-1 versus VE= 1725 ± 0; n = 04; p > 0.05) in the light phase of the diurnal cycle. Thus, our data suggest that orexinergic signaling in the NTSc contribute to CO2 ventilatory response in awake rats in the light phase of the diurnal cycle. Grant 2019/17693-5 São Paulo Research Foundation (FAPESP) and Higher Education Improvement Coordination (CAPES - 001) 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.
Implications of alcohol and western diet on omental adipose metabolic phenotype in rhesus macaques
Authors: Poret Jonquil , Simon Liz , Molina Patricia 
Published: May 2023

Adipose tissue maladaptation is central to metabolic dysregulation seen with calorie-dense, or Western, diets and at-risk alcohol use. We hypothesized that combining these conditions would produce greater adipose tissue maladaptation. The objective of this study was to determine the combined effects of a calorie-dense diet and chronic binge alcohol (CBA) on omental adipose tissue expression of genes that contribute to mitochondrial and metabolic alterations. Omental adipose samples used in the present study were obtained from a subset of animals included in an ongoing parent longitudinal study. Male rhesus macaques were fed ad libitum a high fat, high sucrose diet (HFSD; 41.7% fat and 27% sucrose) for 15.5 months. Starting at 3 months, animals received water (VEH) or CBA (13-14 g/kg/week) through a gastric catheter for the remainder of the study. Omental adipose biopsy samples were collected at the 3- and 7-month timepoints of HFSD feeding and 24 hours following the last alcohol dose. Samples included in this study were as follows: 3-months HFSD (n=5, HFSD), 7-months HFSD + VEH (n=5, VEH/HFSD), 7-months HFSD + CBA (n=5, CBA/HFSD), and bio-banked control-diet fed macaques (n=6, CTRL). Expression of genes associated with glucose and lipid metabolism, insulin sensitivity and mitochondrial health were determined using qRT-PCR. Gene expression of peroxisome proliferator-activated receptor γ, carbohydrate response element binding protein and adiponectin were decreased in HFSD compared to CTRL macaques. HFSD increased gene expression of interleukin 6 compared to CTRL macaques. Gene expression of peroxisome proliferator-activated receptor γ, hormone sensitive lipase and peroxisome proliferator-activated receptor γ coactivator 1-beta were decreased in macaques fed CBA/HFSD compared to VEH/HFSD macaques. Preliminary results indicate HFSD and CBA alter gene expression reflecting omental adipose metabolic and insulin dyshomeostasis and possibly decreased mitochondrial biogenesis and favors an inflammatory milieu. We predict these alterations in omental adipose tissue gene expression may translate into more severe metabolic dysregulation in HFSD fed CBA-treated animals. Supported by NIH/NIAAA P60 AA009803 and 1F31AA028459-01 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.