bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Renin‐Angiotensin Aldosterone System's Effect on Protein Disulfide Isomerase
Authors: Veliz Kenny , Cazares Joshua , Rivera Alicia , Ortiz Rudy , Romero Jose 
Published: June 2021

Disordered activation of the Renin‐Angiotensin‐Aldosterone‐System (RAAS) is associated with hypertension and insulin resistance. The hormones Angiotensin II (Ang II) and Aldosterone (Aldo) are two of its principal effector molecules that have been shown to regulate sodium and volume homeostasis leading to blood pressure control. Ang II has been shown to activate endothelial cells and increase the secretion of extracellular protein disulfide isomerase (PDI). PDI is a multifunctional protein critical to thrombus formation and regulation of reactive oxygen species among other functions. Our group has recently reported that caloric restriction (CR) in rodents leads to increases in Aldo secretion from adrenal zona glomerulosa cells. However, the effects of CR on PDI are unknown. We hypothesize that CR, due to its association with activating RAAS, will lead to increases in the circulating PDI activity. To test our hypothesis, we propose to study the in vitro effects of AngII and Aldo on PDI activity. We will study the in vivo effects of CR on the circulating activity of PDI in Long‐Evans Tokushima Fatty (LETO) and Otsuka Long‐Evans Tokushima Fatty (OLETF). We use two assays to measure PDI activity. In one approach we will use insulin degradation assays. The measurement of circulating PDI activity will be further validated with a fluorescent of Di‐E‐GSSG assay. Initial studies have shown specificity of our assay using the insulin degradation assay and recombinant PDI. Controls of our fluorescent assay are currently underway. We expect that CR will be associated with increased PDI activity.Support or Funding InformationK.V. is supported by an NIH MARC grant R25HL121029 and by the Division of Medical Sciences.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mineralocortidoid Receptor Mediates Uremic Serum‐Induced Increase in Endothelial Cell Dysfunction
Authors: de la Rosa Diego Alvarez , Cazaña‐Perez Violeta , Giraldez Teresa , Navarro‐Gonzalez Juan F. , Kusche‐Virhog Kristina 
Published: June 2021

Patients with chronic kidney disease (CKD) have a markedly increased incidence of cardiovascular disease (CVD) and mortality compared with the age‐matched general population. The high concentration of circulating uremic toxins in CKD patients leads to vascular inflammatory, thereby inducing endothelial dysfunction, which is associated with CVD development and progression. Plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. The aim of our study was to analyze the influence of CKD in the expression of endothelial ion channels and its potential modification by mineralocorticoid receptor (MR) inhibition, which would consequently affect endothelial cell function. To that end we used primary human endothelial cells cultured in medium supplemented with pooled sera from either healthy or uremic patients undergoing dialysis. To obtain a complete profile of ion channel subunit expression in both cellular types, we performed high‐throughput qPCR of 92 ion channel genes using a custom‐designed Taqman low‐density array card. In addition, we characterized the influence of uremic serum on nitric oxide (NO) production and measured cortical stiffness using atomic force microscopy. Our data show that uremic serum potently increased MR expression. In addition, it induced remodeling of ion channel expression patterns, including increased expression of αENaC, a known transcriptional target of MR that promotes cortical stiffness and endothelial dysfunction. Exposure of endothelial cells to uremic serum significantly decreased NO production and produced stiffening of the endothelial cell cortex, which was prevented by inhibition of MR using spironolactone. Our data identifies MR as a possible mediator of uremia‐induced endothelial dysfunction and supports the proposed beneficial effects of MR inhibition during CKD.Support or Funding InformationThis work was supported by a grant from Ministerio de Economía e Innovación (MINECO, grant BFU2016‐78374‐R) to D.A.R.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Timing of Blood Pressure Rhythms Predict Risk of Renal Injury in the Dahl Salt‐Sensitive Rats
Authors: Chen Daian , Booth John N. , Houchin Colton , Colson Jackson C. , Jin Chunhua , Cowley Allen W. , Geurts Aron , Muntner Paul , Young Martin E. , Pollock David M. , Pollock Jennifer S. 
Published: June 2021

Salt‐sensitive individuals have higher susceptibility for dysfunctional diurnal blood pressure rhythms, development of hypertension and renal injury. The aim of this study was to elucidate genetic determinants of diurnal excretion of renal injury markers and timing of systolic BP (SBP) peak and trough patterns in 4 rat models of salt‐sensitivity. We utilized male Dahl salt‐sensitive (SS) rats, NADPH oxidase p67phox knockout in SS (SS.p67phox−/−), introgression of chromosome 13 from Brown‐Norway rats into SS (SS.BN13), and introgression of 16Mbp section of BN13 (SS.BN‐(D13Rat151‐D13Rat197)) in SS (SS.Line26). Male, 12–14 week old rats (n=7–14) were maintained on normal salt (NS; 0.4% NaCl) and then fed high salt (HS; 4% NaCl) diet for 7 days (Dyets, AIN‐76A). Telemetry was used to continuously measure SBP, heart rate and locomotor activity. On NS, 24‐hr SBP was 155.9 ± 0.2 mmHg (SS), 141.6 ± 0.3 mmHg (SSp67phox−/−), 145.5 ± 0.4 mmHg (SS.BN13), and 155.2 ± 0.2 mmHg (SS.Line26). The average 24‐hr SBP in rats on high salt diet was 173.3 ± 0.5 mmHg, 152.2 ± 0.5 mmHg, 158.5 ± 0.6 mmHg, and 171.0 ± 0.6 mmHg, respectively. Eating HS did not change the timing of peak and trough SBP rhythms within each genotype. Furthermore, there were no differences in timing of peak timing of SBP across genotypes on either diet. Similarly, there was no difference in timing of trough SBP across genotypes on NS. However, HS delayed the timing of trough SBP in SS (n=14) by 5.3 hours compared to SS.p67phox−/− (n=12, p<0.001) and by 2.6 hours compared to SS.BN13 rats (n=7, p=0.036). Timing of trough SBP was similar between SS.Line26 (n=12) and SS rats. Heart rate and locomotor activity were not significantly different across genotypes or diets. On HS diet, SS.p67phox−/− (n=8) had lower proteinuria and albuminuria than SS (n=14) and SS.Line26 (n=12) during the active phase (p<0.0001). On HS, proteinuria, albuminuria, and nephrinuria were highest in SS.Line26 compared to SS, SS.p67phox−/−, and SS.BN13 (n=7) during active phase (p<0.01). Excretion of kidney injury marker 1, KIM1, was significantly higher in SS than SS.Line26, SS.BN13, and SS.p67phox−/− (p<0.005). In summary, SS and SS.Line26 rats have delays in the inactive (trough) timing of SBP, which is associated with proximal tubular injury in SS and glomerular injury in SS.Line26 rats. These findings indicate that rat chromosome 13 has a role at least in part, in the timing of SBP and risk of kidney injury in the SS rat.Support or Funding InformationAmerican Heart Association Strategically Focused Research Network ‐ Hypertension (15SFRN2390002)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in the Development of Renal Injury in Obese Dahl Salt‐Sensitive Leptin Receptor Mutant Rats During Prepubertal Obesity
Authors: Poudel Bibek , Shields Corbin Anthony , Cornelius Denise C. , Williams Jan M. 
Published: June 2021

Recent studies show that prepubertal obesity (PPO) is associated with increased risk of renal injury in children. Furthermore, nearly 40% of obese children develop microalbuminuria. Additionally, studies examining the impact of sex on the development of renal injury associated with PPO have been limited. Recently, we reported that, prior to puberty, male Dahl salt‐sensitive leptin receptor mutant (SSLepR mutant ‐ PPO model) rats display proteinuria and podocyte injury by 6 weeks of age independent of hyperglycemia and elevations in arterial pressure. However, female PPO rats were not examined during the same time period. Therefore, in the current study, we investigated whether there were sex differences during the development of renal injury associated with prepubertal obesity. Proteinuria was significantly higher in female and male PPO rats as opposed to the values observed in Control rats at 4 weeks of age (65±12 and 64.7±13 vs 2±1 and 2±0.3 mg/day, respectively, n=4). While we observed minimal increases in proteinuria in Control rats at 8 weeks of age, proteinuria increased to 266.6±65 and 376±56 mg/day in female and male PPO rats, respectively. The kidneys from the PPO rats displayed significant glomerular injury and marked renal fibrosis when compared to the values measured in Control rats. Interestingly, the development of proteinuria and glomerular injury in the PPO model was associated with increased infiltration of CD68+ macrophages expressing Lamp2 and CD36, markers for lysosomes and fatty acid translocase, respectively. Additionally, we assessed renal inflammation via the Bio‐Plex Pro Rat Cytokine 23‐Plex Immunoassay and observed that macrophage inflammatory protein‐3a (MIP‐3a) levels were significantly elevated in both female and male PPO rats (3059±364 and 2545±333 ng/mg of protein, respectively) compared to the values measured in Control rats (1579±291 and 1138±95 ng/mg of protein, respectively). Overall these data indicate that the early development of renal injury in the PPO model might be due to macrophage infiltration stimulating progressive proteinuria independent of hypertension and diabetes.Support or Funding InformationThis study was supported by P20GM104357 and R01 DK109133‐01.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EFFECT OF DENERVATION ON REDOX‐REGULATION IN SKELETAL MUSCLE
Authors: Scalabrin Mattia , Pollock Natalie , McArdle Anne , Jackson Malcolm Joseph , Vasilaki Aphrodite 
Published: June 2021

Changes in skeletal muscle mass and function occur during aging and are accompanied by loss of integrity and stability of the neuromuscular junction. Previous studies from our group have shown a significant increase in the mitochondrial generation of hydrogen peroxide (H202) and other peroxides in denervated muscle fibers. The mechanisms of generation of these peroxides and the effect on muscle responses are unknown. Our aim was to determine the effect of denervation on proteins that may contribute to peroxide release and proteins that regulate redox responses.The Anterior Tibialis (AT) and Extensor Digitorum Longus (EDL) muscles of wild type mice were denervated under anaesthesia by surgical removal of a small section of the peroneal nerve. Western blotting and immunohistochemical techniques were used to examine protein contents. AT and EDL muscles of thy‐1YFP mice, in which YFP expression in neuronal cells allow visualisation of the muscle innervation, were also denervated and used for morphological examination and analysis of muscle mitochondrial peroxide release.Previous work from our group has shown that, following denervation, hydrogen peroxide can be generated by several sources within mitochondria (Pollock et al, Free Rad. Biol. Med 2017) and the current data show that the increased peroxide generation was maintained to 21 days and was associated with a significant increase in Monoamine Oxidase A and NADPH Oxidase components. An increased content of proteins involved in the activation of the NADPH oxidase complex such as Peroxiredoxin 6 and Phospholipase A2 was also observed together with a significant increase in the content of several enzymes involved in the protection of cells against oxidative damage. Oxyblot analysis to assess the levels of carbonylation, showed that by 7 days post‐denervation there was a significant increase in protein carbonylation of low molecular weight (25–35 kDa) proteins. Morphological analysis indicated a progressive significant loss of muscle mass in the AT muscle from 7 days up to 21 days following denervation due to fiber atrophy without fiber loss. These results support the possibility that (at least initially) the increase in peroxide production may stimulate adaptations to protect the muscle fibers but, together with data on structural changes indicating significant fiber atrophy from 7 days after denervation, increased peroxide generation over the longer term may activate degenerative processes, such as apoptosis of the denervated muscle fibers.Support or Funding InformationThis project was funded by the US National Institutes of Health (NIA) and the Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Consecutive, Long‐Duration Hyperoxic Water Immersions on Neuromuscular Performance in Well Trained, Male Divers
Authors: Myers Christopher , Kim Jeong‐Su , Florian John 
Published: June 2021

PURPOSEThe main objective of this study was to investigate the physiological effects of single and repetitive diving‐induced hyperoxic conditions on neuromuscular performance at 1.35 atmospheres absolute (ATA). We hypothesized that following five days of consecutive, resting, long‐duration hyperoxic water immersion (WI)s, neuromuscular performance would be reduced with a longer recovery period in comparison to normoxic WIs at 1.35 ATA.METHODSThroughout a dive week (DW), twenty‐eight healthy, active male divers [30±1 (24–43)years; mean ± SEM] completed five consecutive 6‐hour resting WIs with 18‐hour surface intervals while breathing compressed atmospheric air (Air: n=15) or 100% oxygen(O2:n=13) at 1.35 ATA. Skeletal neuromuscular performance was assessed immediately before and after each WI, and 24 and 72 hours after the final WI. Assessments included knee extension and elbow flexion maximum voluntary isometric contractions (MVIC) and maximal isokinetic (IK) contractions, as well as measurement of maximum handgrip strength (MHG). Simultaneously, surface electromyography (sEMG) amplitude of the vastus lateralis, rectus femoris, vastus medialis, biceps brachii, and brachioradialis was measured.RESULTSSignificant decreases were seen in maximal strength performance on WI 3 (MVIC knee extension: 3.4%, p<0.001; O2: 4.3%, p=0.016; MVIC elbow flexion: 3.5%, p=0.002, combined group result) with recovery occurring by WI5. The O2 group knee extensor neuromuscular activation decreased by 10% throughout the DW and remained reduced by 14% through the 72‐hr post‐WI. The Air group neuromuscular activation increased throughout the DW but returned to baseline by 72‐hr post‐dive. Combined group maximal IK elbow flexion and MHG strength performance decreased by 4% and 5%, respectively, throughout the DW (WI1> WI3 and WI5, p<0.001).CONCLUSIONConsecutive, resting, long‐duration normoxic WIs cause noticeable decrements in muscular strength performance after three days of WIs with recovery seen by 24‐hr post‐WI. Hyperoxic WIs caused significant reductions to neuromuscular activation. Future research should examine the causes of hyperoxia‐induced decreased neuromuscular activity.Support or Funding InformationOffice of Naval Research (ONR) Award Number N000141612112 and NAVSEA DSBDP N0002416WX02277This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Work of Breathing in Obese Men with and without Dyspnea on Exertion
Authors: Bernhardt Vipa , Bhammar Dharini M. , Marines‐Price Rubria , Babb Tony G. 
Published: June 2021

INTRODUCTIONBreathlessness during exercise, or dyspnea on exertion (DOE), is a common complaint in otherwise healthy obese adults. It is possible that the higher perception of breathlessness is due to a higher work of breathing. Thus, we investigated whether obese men with high DOE (+DOE) have a higher work of breathing (i.e., oxygen cost) than obese men with a low DOE (−DOE).METHODS27 obese men underwent underwater weighing and a 6‐min constant load submaximal cycling exercise at 105 W. They also performed eucapnic voluntary hyperpnea (EVH) to determine the oxygen cost of breathing. Participants were classified as +DOE, if their Rating of Perceived Breathlessness (RPB, Borg 0–10 scale) was ≥ 4 (n = 16) and as −DOE if RPB was ≤ 2 (n = 11) during minute 6 of the exercise test. The oxygen cost of breathing was obtained by calculating the slope of the oxygen uptake (ml/min) vs. ventilation (L/min) relationship at rest and during EVH at 60 and 90 L/min. RPB was also collected during the last minute of each EVH trial. Following the 90 L/min EVH trial, participants were asked to choose the “top 3 descriptors that best describe[d] the respiratory sensations [they] felt during the test” from a list of 15 descriptors. Data were analyzed between groups by independent t‐test.RESULTSThere were no significant differences between +DOE and −DOE groups in age, BMI, or body fat percentage, respectively (+DOE: 35 ± 6 yr, 36 ± 5 kg/m2, 39 ± 5%; −DOE: 32 ± 6 yr, 35 ± 3 kg/m2, 37 ± 6%; mean ± SD, p > 0.05). Breathlessness ratings during each level of EVH was significantly greater in the +DOE than the −DOE group (p < 0.01). However, there was no significant difference in the oxygen cost of breathing between +DOE (2.05 ± 0.63 ml/L) and −DOE (1.99 ± 0.78 ml/L, p > 0.05). Eleven of the 16 men +DOE felt that their breathing required effort or work (only 3 of the 11 men −DOE).CONCLUSIONSThe otherwise healthy obese men who rated higher breathlessness during exercise also perceived higher breathlessness during the EVH trials. The increase in the intensity of breathlessness was not due to an increased oxygen cost of breathing. Even though the measured work of breathing was not different, the +DOE group more frequently described their breathing to require more work/effort; this perception of effort may be due to changes in neural transmission in the brain, such as a reduced gating of respiratory sensations related to the work of breathing.Support or Funding InformationSupported by NIH Grant R01 HL096782 and King Charitable Foundation Trust.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cough response to sulfur dioxide inhalation challenge is enhanced by tumor necrosis factor alpha: a primary role of vagal bronchopulmonary C‐fibers
Authors: Lin Ruei‐Lung , Zhang Cheng , Khosravi Mehdi , Lin An‐Hsuan , Athukorala Ashami , Lee Lu‐Yuan 
Published: June 2021

Tumor necrosis factor alpha (TNFα), a pro‐inflammatory cytokine, plays a significant role in the pathogenesis of asthma. We recently reported that TNFα pretreatment elevated the sensitivities of vagal bronchopulmonary C‐fibers and silent rapidly adapting rectors (RARs) to capsaicin (Front. Physiol. 2017). In this study, we investigated the effect of TNFα on cough response to sulfur dioxide (SO2), a common irritant gas, and the relative contributions of these vagal afferents. Our results showed: 1) Inhalation of SO2 (300 and 600 ppm; 8 min each) consistently elicited coughs in a concentration‐dependent manner in awake mice moving freely in a recording chamber; coughs were recorded via telemetry sensors implanted in the intrapleural space. The cough frequencies during and immediately after the SO2 inhalation challenges increased markedly in the same animals after TNFα (10 μg/ml; 0.03 ml) was administered into the lung by intratracheal instillation, and this increase in cough sensitivity sustained for >7 days after the TNFα pretreatment. In contrast, the cough response to SO2 inhalation challenges did not change after pretreatment with vehicle (0.03 ml of PBS) in a matching group of control mice. 2) In single‐fiber recording experiments in anesthetized mice, the same SO2 inhalation challenges (for 8 min) evoked a pronounced stimulatory effect on C‐fiber afferents, reaching a peak in 1–4 min. The increased fiber activity was concentration dependent and lingered for several more minutes after the termination of SO2 challenge. This stimulatory effect of SO2 was significantly elevated in the TNFα‐treated mice. 3) The same SO2 inhalation challenges, either 300 or 600 ppm, did not activate any of the silent RARs in vehicle‐treated mice, and only 600 ppm SO2 caused a very weak stimulation in 2 out of 7 of these silent RARs in TNFα‐treated mice. 4) Inhalation of SO2 (300 or 600 ppm) consistently induced an inhibitory effect on both slowly adapting receptors and phasic RARs; these afferents ceased to discharge completely in 1–5 min after the onset of SO2 (600 ppm) inhalation challenge, and a majority of them slowly returned to controls after resuming air breathing for >1 hr. No detectable difference in this inhibitory effect was found between TNFα‐ and vehicle‐treated mice. In conclusion, the cough response to SO2 inhalation challenge is enhanced by the TNFα pretreatment in wake mice, and an increase in the bronchopulmonary C‐fiber sensitivity to SO2 is primarily responsible.Support or Funding InformationNIH grant AI123832This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of distention in swallow phase transition
Authors: Huff Alyssa , Reed Mitchell , Pitts Teresa 
Published: June 2021

The effect of pharyngeal and esophageal distention on swallow phase transition has not been fully elucidated. In quadrupeds we hypothesize pharyngeal to esophageal (P:E) ratio is dependent on distention of the pharynx and/or esophagus to trigger a phase transition. To this effect videofluoroscopy was performed on 8 cats using liquid and puree consistencies laced with 40% barium. Awake cats were given 30 seconds after food/liquid presentation to initiate eating/drinking. Using MicroDicom viewer software (MicroDICOM; Sofia, Bulgaria) diameter was calibrated using an object placed in the viewing field (i.e. dime). The diameter of the pharynx, upper esophageal sphincter opening, and bolus size in the esophagus were measured. There was a significant difference between the tolerated pharyngeal distention between liquid (9.5 ± 1.9 mm) and puree (12.6 ± 2.5 mm) boluses (p=0.01), as well as esophageal distention between liquid (6.5 ± 1.9 mm) and puree (8.3 ± 2.2) boluses (p<0.05). The average distention of the UES was not significantly different (p> 0.05) with a diameter of 7.8 ± 2.0 mm for liquid versus 9.0 ± 2.0 mm for puree. The ratio of pharyngeal to esophageal phase swallows range from 2–6 in liquid boluses and 1–3 in puree boluses. The variable pharyngeal to esophageal phase ratio supports the hypothesis that transition through each phase of swallow is driven by distention of the pharyngeal and esophageal walls and not by a set P:E ratio.Support or Funding InformationSupported by R00‐ HL 111215 and The Kentucky Spinal Cord and Head injury Trust.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.