bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breathing 5% carbon dioxide for 1 minute increases cerebral blood flow during lower body negative pressure
Authors: Harrell John , Beri Rachel , Edelsztein Lail , Muriithi Andrew , Pollock Ross 
Published: May 2024

Objective: Lower body negative pressure (LBNP) is an established surrogate of hypergravity to investigate responses to central hypovolemia, including the reduction in cerebral blood flow. Increased inspired carbon dioxide (CO2) causes cerebrovascular dilation and increases cerebral blood flow. We aimed to determine whether breathing 5% CO2 for 1 minute increased cerebral blood flow during LBNP. We hypothesized 5% inspired CO2 would increase cerebral blood flow during LBNP. Methods: We collected data from 15 (9 M/6 F, 31±8 yr, 25.6±3.2 kg/m2) healthy individuals. Subjects breathed room air or a mix of 5% CO2, 21% oxygen, balance nitrogen gas for 1 minute prior to initiation of 2 minutes of -60 mmHg LBNP and throughout the duration of LBNP. We allowed a 2-minute wash-out between trials. We measured middle cerebral artery velocity (MCAv) with transcranial Doppler ultrasound and continuous, non-invasive blood pressure (MAP) with a finger plethysmograph. We corrected MCAv for MAP and present it as cerebrovascular conductance index (CVCi). We also measure ventilation and gas exchange with a pneumotachometer and gas analyzer. Results: All measured variables were similar prior to the initiation of room air and 5% CO2 prebreathe ( p > 0.05). Inspired (1±1 vs. 36±1 mmHg) and end-tidal (38±4 vs. 47±3 mmHg) CO2 were greater during the 5% inspired CO2 trial ( p < 0.05, main effect of gas). LBNP caused an increase in heart rate, decrease in stroke volume, decrease in cardiac output, and an increase in total peripheral resistance ( p < 0.05, main effect of LBNP). These variables were similar regardless of inspiratory gas. MCAv (40±16 vs. 53±19 cm/s), MAP (94±10 vs. 99±11 mmHg), and CVCi (0.46±0.22 vs 0.56±0.24 cm/s/mmHg) were all greater during the 5% inspired CO2 trials ( p < 0.05, main effect of gas). Discussion: Breathing a mixture of 5% CO2 for 1 minute increased cerebral blood flow and blood pressure during a mimic of hypergravity stress. Despite technical challenges of integration into high-performance aircraft, increasing inspired CO2 could contribute to better tolerance to hypergravity stress. Funding was provided by the Air Force Offce of Scientific Research and King’s College London. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Epigenetic changes to the carotid body drive hypertension in perinatal nicotine exposed rats
Authors: Zhu Fengli , Liu Jie , Rehan Virender , Jendzjowsky Nicholas 
Published: May 2024

Background: Epigenetic changes can be shaped by a wide array of environmental cues as well as maternal health and behaviors. One of the most detrimental behaviors to the developing fetus is nicotine exposure. Perinatal nicotine exposure remains as a significant risk factor for cardiovascular health and in particular, hypertension, as it has been shown to alter angiotensin signaling. Hypothesis: We hypothesized that perinatal nicotine exposure alters carotid body angiotensin signaling to induce hypertension in adult life. Methods: Pregnant Sprague-Dawley rats were exposed to nicotine (2mg/kg SQ, or PBS- control) from estrous day 6 to post-natal day (PND) 21. Experiments on pups took place from PND 56-90. Carotid bodies were harvested pooled together for RNAseq and confirmation of unbiased transcriptomics was conducted with qPCR. Blood pressure was measured with indwelling telemetry. ELISA assessed serum angiotensin. PC12 cells were used a surrogate for carotid body glomus cells and were used for calcium imaging. Results: Unbiased RNAseq of carotid bodies from nicotine exposed pups compared to saline control pups showed that KEGG pathways with significant angiotensin signaling components including Neuroactive ligand-receptor interaction (Log2FC=2.4, p=7.5x10−8) and Dopaminergic synapse (Log2FC=2.3, p=0.0007) were significantly upregulated. qPCR of carotid bodies demonstrated that Angiotensin II type 1 receptor (56%↑), Angiotensin II type 2 receptor (15%↑) and TRPV1 channels (63%↑) were upregulated in nicotine exposed pups compared to controls. Blood pressure measured in nicotine exposed pups was suppressed 1 day after bilateral carotid body denervation. Circulating angiotensin assessed from serum was similar between nicotine exposed and control pups. Calcium imaging of PC12 cells showed that nicotine significantly increased spike frequency in response to nicotine (0.2mg/ml). Incubation with nicotine + Angiotensin (50ng/ml) did not further increase spike frequency. This increased excitation was suppressed with losartan (3μM), AMG9810 (TRPV1 antagonist, 10μM) and combined blockade (p<0.05). Conclusion: Our data demonstrate that adverse maternal behaviors produce epigenetic changes to carotid bodies of offspring resulting in neurogenic hypertension. The epigenetic changes involve an Angiotensin-Angiotensin II type 1 receptor-TRPV1 channel axis in the carotid body without any significant systemic changes. We suggest carotid body modulation may have a significant health impact on offspring with adverse perinatal environmental exposures. UCOP TRDRP T32IP4707, T32KT4708. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
APOE and sex impacts functional recovery after cervical spinal cord injury
Authors: Taylor Chase , Sunshine Michael , Devine Caroline , Patel Mohit , Johnson Lance , Alilain Warren 
Published: May 2024

Genetic factors are key to understanding recovery following spinal cord injury (SCI). Prior work conducted in our laboratory demonstrated that APOE genotype impacts respiratory plasticity after cervical SCI. Specifically, female mice expressing the APOE4 allele had impairments in their ability to generate and maintain robust diaphragmatic activity following cervical SCI and intermittent hypoxia treatment relative to APOE3 counterparts. Subsequently we showed that different APOE alleles leads to altered neural respiratory control even without a spinal cord injury and that the effect is sex dependent. To extend these findings, we are now investigating the impact of APOE genotype and sex on locomotor and respiratory motor recovery in a humanized APOE knock-in mouse model homozygous for either the APOE3 and E4 alleles. Further, we examined how genotype and sex effected plasticity and serotonin levels below the lesion. We hypothesized that animals with the APOE4 allele will demonstrate impaired recovery following SCI across all measures. We performed a left C2 hemisection injury on male and female mice of both APOE3 and APOE4 genotype (n = 8/group). We recorded whole body plethysmography and CatWalk gait analysis weekly beginning at pre-injury through three weeks post injury. Consistent with our previous findings male APOE3 mice responded better than APOE4 counterparts during respiratory challenge even following SCI. Specifically APOE3 male mice showed greater improvements in respiratory rate during both normoxia and hypoxia challenge at early timepoints following injury. Interestingly during catwalk gait analysis APOE4 male mice recovered function faster than APOE3 counterparts in the weeks following SCI. This work is critical because it lays the foundation for understanding how diverse genotypes in the clinical SCI population may indicate the need to personalize treatment for individuals following injury. AG065220 AG060056 Nielsen Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Chronic circadian stress raises mean arterial pressure in male, but not female, Bmal1-knockout rats
Authors: Rhoads Megan , Latimer Mary , Monroe Brianna , Howard Kameron , Pollock David 
Published: May 2024

Shiftwork and other forms of circadian disruption are associated with an increased risk of cardiovascular and kidney disease, however, the mechanisms driving these associations have yet to be elucidated. It has been suggested that dyssynchrony between the endogenous molecular clock and the external environment during shiftwork may be connected with the development of cardiorenal pathologies and the dysregulation of blood pressure (BP). Brain and muscle arntl-like protein 1, or Bmal1, is a core component of the molecular clock. Loss of Bmal1 in both male and female rats results in lower BP compared to wild-type (WT) littermate controls. We hypothesized that Bmal1 is necessary for the acclimation to circadian stress induced by chronic circadian stress (CCS). Telemeters were surgically implanted in the abdominal aorta of 12-14 week old rats. After a 2 week recovery, animals were placed in a light-controlled room on a 12:12hr light/dark cycle. After 1 week acclimation, lights were phase-advanced 6hrs every week for 4 weeks. Telemetry data was collected for 2 minutes every 10 minutes each hour at 1000 samples/second and analyzed using cosinor analysis. The MESOR of mean arterial pressure (MAP) was similar pre- and post- CCS in male WT rats (n=8, 107±1 vs. 109±1 mmHg; 2-way ANOVA, p>0.05) and in female WT rats (n=9, 110±1 vs. 112±2 mmHg; p>0.05). Male Bmal1-KO rats (n=9) had higher MAP MESOR after CCS (103±1 vs 108±1mmHg; p<0.05), but female Bmal1-KO rats (n=6) had no change in MAP MESOR after CCS (100±2. vs 100±2 mmHg, p>0.05). MAP amplitude was similar between WT and KO males before- (6.5±0.7 vs. 5.2±0.8 mmHg) and after-CCS (5.1±0.4 vs. 5.3±0.4 mmHg, p>0.05). WT and KO females had similar MAP amplitude before- (7.2±0.6 vs 5.5±0.9 mmHg) and after-CCS (5.7±1.1 vs. 5.6±0.6, p>0.05). In summary, loss of Bmal1 combined with circadian stress resulted in higher BP in a sex- dependent manner. Despite having lower blood pressures pre-CCS, male Bmal1-KO rats had higher MAP after CCS while female Bmal1-KO rats were protected from increased BP. This suggests that Bmal1, a crucial component of the molecular clock, has a sex-specific role in BP regulation and the response to stress. This work is supported by NIH TL1DK139566-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Chronic central leptin administration attenuates kidney dysfunction and injury in a model of ischemia/reperfusion-induced acute kidney injury
Authors: Luna-Suarez Emilio , da Silva Alexandre , Wang Zhen , Mouton Alan , Dai Xuemei , Larson Kylie , Ladnier Emily 
Published: May 2024

Kidney disease occurs in approximately 15% of the adult population, accounting for 37 million people in the US alone. Lack of blood flow is a major driver of kidney injury and no therapeutic modalities have shown substantial effcacy in treating ischemia-induced acute kidney injury (AKI). We recently demonstrated that activation of the brain leptin-melanocortin system dramatically improves cardiomyocyte mitochondrial function, energy metabolism and contractility, preserving cardiac function and preventing progression of heart failure following myocardial infarction and ischemia/reperfusion injury. In the present study we examined whether chronic intracerebroventricular (ICV) leptin administration protects the kidney against ischemia/reperfusion (I/R)-induced AKI. Twelve-week old male rats were implanted with an ICV cannula into the right lateral ventricle and 8-10 days after surgery, leptin (0.021 mg/hr, n=8) or saline vehicle (0.5 ml/h, n=8) was infused via osmotic minipump connected to the ICV cannula for 12 days. On day 8 of leptin or vehicle infusion, rats were submitted to unilateral ischemia/reperfusion (UIR) by clamping the left pedicle for 30 min. To control for leptin-induced reductions in food intake, the vehicle group was pair-fed (UIR-PF) to match the same amount of food consumed by leptin-treated (UIR-Leptin) rats. On the 12th day of leptin or vehicle infusion (i.e. 4th day after AKI), single-left kidney glomerular filtration rate (GFR) was measured, blood samples were collected to quantify white blood cells, and kidneys were collected for histological assessment of injury. Chronic leptin infusion reduced body weight by 20±1% compared to only 10±1% reduction in UIR-PF. UIR-Leptin rats also showed reduced right and left kidney weights (right: 1040±24 vs. 1281±36 and left: 1127±71 vs. 1707±45 mg, for UIR-Leptin and UIR-PF, respectively). Leptin infusion improved GFR (0.50±0.06 vs. 0.13±0.03 ml/min/g KW) and reduced kidney injury scores. Leptin treatment also increased circulating white blood cells count compared to UIR-PF rats (16.3±1.3 vs. 9.8±0.6 k/mL). Thus, leptin, via its actions on the central nervous system, confers significant protection against major kidney dysfunction and damage in a model of ischemia/reperfusion-induced AKI. NIH grants: (1R0DK1121411 (do Carmo), 1R0HL1630376 (da Silva/do Carmo), P20GM104357 (Hall), P30GM149404 (Hall) and U54GM115428 (Hall)). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The Epithelial Na+ Channel Is a Zn2+ Sensitive Renal Na+ Reabsorption Pathway that Mediates Zn2+ Deficiency-induced Hypertension
Authors: McMichael Kelia , Yesomi Wenegieme Tara , Waite Aston , Williams Clintoria , McMichael Kelia 
Published: May 2024

Background: Zinc (Zn2+) deficiency (ZnD) is comorbid with many chronic diseases including kidney disease and diabetes. Individuals in these vulnerable populations have a higher prevalence of hypertension. Recently, we reported that ZnD induces hypertension by promoting renal Na+ reabsorption. However, the renal Na+ reabsorption mechanisms involved continue to be identified. The renal epithelial Na+ channel (ENaC) plays an essential role in regulating whole-body Na+ and water balance and is involved in hypertension. We hypothesize that ENaC is a Zn2+-sensitive channel that mediates ZnD-induced hypertension. Experimental Design: To establish the role of ENaC in ZnD-induced hypertension, WT C57Bl/6 mice were switched from a Zn2+ adequate to a Zn2+ deficient diet for 10 weeks. During weeks 9 and 10, mice were treated with benzamil, an ENaC inhibitor. Systolic blood pressure (BP) was monitored by tail-cuff plethysmography; Renal ENaC expression was examined by immunohistochemistry and Western blot. To authenticate the Zn2+ sensitivity of ENaC, mouse distal convoluted tubule cells (mDCT) were treated with a Zn2+ chelator (TPEN) or vehicle (ethanol) for 24 hours. A subset of TPEN-treated cellular monolayers were supplemented with Zn2+ for 24 hours to replete intracellular Zn2+. Cellular ENaC expression was examined by Western blot analysis. Results: 1) Blood pressure: Compared to Zn2+ adequate mice (101.4 mm Hg ± 4.225), Zn2+ deficient mice had increased BP (154.6 mm Hg ± 2.422). However, benzamil treatment lowered BP (115.0 mm Hg ± 4.626) of Zn2+ deficient mice. 2)Immunohistochemistry: Next, Zn2+ effects on ENaC expression were examined. In Zn2+ deficient mice, αENaC protein abundance significantly increased compared with Zn2+ adequate mice. 3) Western blot analysis: To directly investigate Zn2+effects on ENaC expression, in vitro studies were performed using mDCT cells. Western blot analysis showed that TPEN-induced ZnD stimulated both αENaC and βENaC protein expression. Conclusion: Collectively, our findings reveal that (1) ENaC is a Zn2+ sensitive renal Na+ reabsorption pathway and (2) ENaC mediates ZnD-induced hypertension. Significance: Understanding the renal mechanisms by which Zn2+ regulates blood pressure may have an important therapeutic impact on hypertension. Funding: R21 DK119879, R01 DK-133698 (National Institute of Diabetes and Digestive and Kidney Diseases); R25DK078381 (NIH NIDDK STEP-UP program);1742339 (National Science Foundation ASK Program). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Blood Pressure and Central Arterial Stiffness before and after a 161-km Ultra-Endurance Race
Authors: Vondrasek Joseph D. , Jeong Soolim , El-Kurd Omar B. , Linder Braxton A. , Stute Nina L. , Dormeier Christin , Bissen Thomas G. 
Published: May 2024

BACKGROUND: Competing in ultra-endurance running events (>42.2 km) is a tremendous physiological stressor. Training for and competing in these events may be detrimental to cardiovascular (CV) health. However, previous findings on acute changes in key CV health measures like blood pressure (BP) and central arterial stiffness after a race remain equivocal. Therefore, we aimed to characterize the acute CV response to an ultra-endurance race. We hypothesized that BP would decrease while central arterial stiffness would increase following the race. Methods: We measured supine BP with an automated brachial cuff and carotid-to-femoral pulse wave velocity (cfPWV - index of central arterial stiffness) with applanation tonometry (SphygmoCor XCEL, AtCor Medical) among 41 finishers (9F/32M; Age: 44 ± 10 years; BMI: 22.7 ± 1.8 kg/m2) of the 2023 161-km Western States Endurance Run (WSER). Measures were taken 1–3 days before (pre) and ≤1 hour after race completion (post). We present data as mean ± SD after confirming normality using Shapiro-Wilk tests (α ≥ 0.05). We assessed differences between pre- and post- systolic BP (SBP), mean BP (MBP), diastolic BP (DBP), cfPWV, and cfPWV normalized to MBP using paired, two-tailed t-tests (α < 0.05). The magnitude of the difference between time points was represented as Cohen’s d ( d) effect sizes. Results: After the race, there was a significant decrease in SBP (129 ± 9 vs. 122 ± 10 mmHg, P < 0.001, d = 0.78), MBP (94 ± 7 vs. 89 ± 10 mmHg, P < 0.001, d = 0.58), and DBP (77 ± 7 vs. 74 ± 8, P = 0.02, d = 0.38) but no change in cfPWV (6.4 ± 1.0 vs. 6.2 ± 0.8 m/s, P = 0.10, d = 0.26) or cfPWV normalized to MBP (0.07 ± 0.01 vs. 0.07 ± 0.01 (m/s)/mmHg, P = 0.83, d = 0.00). CONCLUSION: We found that systolic, mean, and diastolic pressure were all lower after the 161-km WSER, but cfPWV did not change. These findings suggest that running a 161-km ultra-marathon race acutely lowers BP but does not affect central arterial stiffness. Further research is needed to understand the effect of chronic ultra-endurance training and competition on cardiovascular health. FUNDING INFORMATION: Western States Endurance Run Medical Research Program (GJG), National Institutes of Health K01HL160772 (JCW), American Heart Association 23CDA1037938 (JCW). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Whey Protein Isolate Supplementation Effects on Cortisol Awakening Response, Profile of Mood States, and Heart Rate Variability
Authors: Oldham Michael , Ben-Ezra Vic , Biggerstaff Kyle , Mills Nate , Brisebois Matthew , Castleberry Todd , Deemer Sarah 
Published: May 2024

INTRODUCTION: Decreases in heart rate variability (HRV), disruptions in cortisol awakening response (CAR), and changes in Profile of Mood States (POMS), have been associated with fatigue and strenuous physical exercise. Whey protein isolate can affect stress responses. PURPOSE: To determine the effects of whey protein isolate supplementation on CAR, POMS, and HRV after strenuous exercise. Methods: Eleven recreationally active women (19 ± 2 yrs) completed a double blinded, crossover trial. Placebo was maltodextrin (PL), intervention was 25 g of maltodextrin and 25 g of whey protein isolate (WH). Exercise was 30 min at 70-75% VO2peak (21.7 ± 0.1 ml/kg/min), 5 min rest, and 30 s Wingate anaerobic test (WAnT). HRV and POMS were recorded. Repeated measures ANOVA were used to determine differences (p < 0.05) in salivary cortisol AUCg, POMS, HRV, and WAnT fatigue index (FI). Pearson correlation and multiple regression determined associations between CAR, POMS, and HRV to FI. Results: Cortisol AUC were significantly different (p = 0.033) between PL (33.4 ± 2.0 μg*hr/dL) and WH (30.9 ± 0.8 μg*hr/dL), with no significant differences in POMS, HRV, or FI (p > 0.05). Significant Pearson correlation on Day 3 during the PL, between POMS and FI (r = -.582, p = 0.030). Neither CAR, POMS, nor HRV was able to predict FI (all p > 0.05). CONCLUSIONS: Whey protein isolate may decrease CAR, but may have no effect on POMS, HRV, or FI, and no effect on short-duration sprint cycling performance, and or reduction in central fatigue may be minimal. No supporting funding. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Impact of Respiratory Muscle Training on Exercise Tolerance in Hypobaric Hypoxia
Authors: Ferguson Scott , Miller Michael , Yeager Luke , Wislowski Annie , Subudhi Andrew , Roach Robert 
Published: May 2024

Hypoxia and certain chronic diseases can intensify the work of breathing, potentially impacting the muscle hyperemic response during exercise and overall exercise performance. Respiratory muscle training (RMT) has been observed to decrease perceived effort under hypoxic conditions; however, it remains unclear if RMT boosts exercise performance in acute hypoxia. We investigated whether 4 weeks of RMT could enhance maximal and submaximal exercise performance in hypoxia (PB=425 mmHg, ~4876 m). Seven adult males underwent a 250 kJ submaximal (RPE 15-17) cycling trial in hypoxia, followed by an incremental test to maximal exertion. After 4 weeks of RMT under normoxic conditions, these tests were repeated in hypoxia. Although six of the participants displayed improvements in submaximal exercise performance, these numerical differences failed to reach statistical significance. However, RMT did raise VO2max peak power (Pre-RMT: 242.62 ± 35, Post-RMT: 251.85 ± 38 W, p=0.04). Moreover, even with an increased HR during the submaximal exercise trial after RMT (Pre-RMT:154.14 ± 16, Post-RMT: 160.86 ± 12, p<0.05), the RPE showed no significant difference during the test (Pre-RMT: 17.43 ± 0.79, Post-RMT: 17.43 ± 0.53, P>0.05). Despite this, no substantial increase in hypoxic submaximal exercise performance was observed, likely due to the small sample size. These findings suggest RMT might increase hypoxic exercise tolerance by reducing perceived exertion for a given HR. This work was supported by funding from the United States Special Operations Command (USSOCOM) and the National Institutes of Health (2L30HL134123-03). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.