bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Cytokines and Blood Pressure after Renal Denervation in 2‐Kidney, 1‐Clip Hypertensive Rats
Authors: Lauar Mariana Ruiz , Van Helden Dusty , Banek Christopher T , Evans Louise C , Menani Jose Vanderlei , Osborn John W 
Published: June 2021

Hypertension (HTN) is a multifactorial disease that affects one third of the population of western countries. Although 95% of cases are of unknown origin (i.e., primary HTN), it is well established that renal ischemia results in secondary renovascular HTN. Experimental renovascular HTN is induced in rats by placing a silver clip on the left renal artery creating a stenosis, which decreases renal perfusion pressure and increases renin release from the clipped kidney (2K1C‐HTN). Previous studies indicate a role of renal nerves in 2K1C‐HTN since renal denervation (RDN) attenuates HTN in 2K1C‐rats. Moreover, activation of the sympathetic nervous system in this model is associated with inflammation in the hypothalamus, a key site for regulation of sympathetic activity that also receives input from afferent renal nerves. In the present study, we tested the hypothesis that renal nerves modulate the levels of hypothalamic proinflammatory cytokines and mean arterial pressure (MAP) in 2K1C rats. Male Sprague‐Dawley rats (150–180 g, n=2–4/group) received a clip on the left renal artery to generate 2K1C HTN and were instrumented with telemeters to measure MAP. Four weeks later rats underwent RDN (2K1C‐RDN) or sham (2K1C‐sham) surgery of the clipped kidney and MAP measurement continued for the following 2 weeks. Rats were then euthanized and brains quickly removed for subsequent measurement of hypothalamic cytokine content. Preliminary data demonstrated that MAP was lower 2K1C‐RDN (157±20 mmHg) than 2K1C‐sham (175±7 mmHg) rats. RDN also tended to decrease hypothalamic cytokine content. IL‐1β was 25±3 pg/mg in 2K1C‐RDN compared to 151±66 pg/mg in 2K1C‐sham rats. IL‐6 content was 24±19 pg/mg in 2K1C‐RDN vs. 39±0.5 pg/mg in 2K1C‐sham rats. The results suggest that RDN may decrease hypothalamic inflammation in 2K1C hypertensive rats and this may be one mechanism by which RDN decreases MAP in this model.Support or Funding InformationFAPESP (2018/11221‐1), PROPE/FUNDUNESP and NIH R01 HL116476.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Role of Vascular Smooth Muscle RhoBTB1 in Hypertension
Authors: Fang Shi , Mukohda Masashi , Wu Jing , Agbor Larry N. , Nair Anand R. , Ibeawuchi Stella‐Rita , Hu Chunyan , Liu Xuebo , Lu Ko‐ting , Guo Deng‐Fu , Davis Debbie , Keen Henry L. , Quelle Fredrick W. , Sigmund Curt D. 
Published: June 2021

RhoBTB1 is an atypical GTPase, which is associated with human hypertension according to a genome‐wide association study. However, the physiological and molecular role of RhoBTB1 is not well understood. Previously, we showed that aortic RhoBTB1 is downregulated in two hypertension models including systemic angiotensin II (Ang II) infusion and vascular smooth muscle (VSM) specific expression of human hypertension causing dominant negative PPAR gamma mutant P467L (S‐P467L). To achieve RhoBTB1 genetic complementation, we generated mice with VSM specific, tamoxifen inducible RhoBTB1 (S‐RhoBTB1) expression. Previous studies showed that S‐RhoBTB1 mice are resistant to Ang II‐induced hypertension. In the current study, we are investigating whether restoration of RhoBTB1 expression is sufficient to reverse established Ang II‐induced hypertension. S‐RhoBTB1 mice received systemic Ang II‐infusion (490ng/kg/min) for two weeks before tamoxifen injection. However, S‐RhoBTB1 did not reverse Ang II‐induced elevated blood pressure. Aorta and carotid artery still exhibited impaired vasodilation to acetylcholine and sodium nitroprusside. Pulse wave velocity was elevated in both S‐RhoBTB1 and non‐transgenic mice receiving Ang II infusion, indicating a persistence of arterial stiffness. Unlike Ang II infusion, restoration of RhoBTB1 was sufficient to reverse hypertension, vascular dysfunction and arterial stiffness in S‐P467L mice. In S‐P467L mice aorta, the activity of phosphodiesterase 5 (PDE5), an enzyme that degrades vasodilator cGMP, was elevated in S‐P467L and normalized upon RhoBTB1 restoration. We transfected HEK293 cells with RhoBTB1 and PDE5 and found, using co‐immunoprecipitation, that PDE5 physically interacts with RhoBTB1. Moreover, RhoBTB1 increased PDE5 ubiquitination in a Cullin3‐dependent manner. Hence, a potential molecular mechanism underlying RhoBTB1's cardiovascular protective role is that RhoBTB1 acts as a substrate adaptor for Cullin3‐RING dependent ubiquitin ligase. In conclusion, RhoBTB1 might be a novel hypertension therapeutic target, which requires further characterization.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Stabilizing Ryanodine Receptor with Chronic Dantrolene Treatment Does not Affect Hypertension, but Attenuates Atrial Fibrillation Inducibility under Sympathetic Stimulation in Spontaneously Hypertensive Rats
Authors: Lee Jae S , Li Ying , Gerdes A. Martin , Zhang Youhua 
Published: June 2021

IntroductionRyanodine receptor (RyR) dysfunction in skeletal muscle (RyR1) is linked to malignant hyperthermia, and in cardiac muscle (RyR2) is associated with cardiac arrhythmias and heart failure. We hypothesized that RyR dysfunction in vascular smooth muscle (RyR 1,2 and 3) could increase vascular resistance and blood pressure by increasing intracellular calcium level. RyR dysfunction may also contribute to increased atrial fibrillation (AF) in hypertension. Thus, stabilizing RyR function with chronic dantrolene treatment may attenuate hypertension development and AF inducibility in spontaneously hypertensive rats (SHR).MethodsMale SHR (16 week‐old) were randomized into vehicle‐ (n=10) and dantrolene‐treated (10mg/kg/d, n=10) groups for 4‐weeks. Male Wistar Kyoto (WKY, n=10) rats served as controls. Tail‐cuff blood pressures were recorded before treatment, and at 1‐week, 3‐week during the treatment period. At the end of the 4‐week treatment period, direct blood pressure, echocardiography and hemodynamics were recorded. Atrial fibrillation inducibility tests were performed at baseline and under sympathetic stimulation (SS) with isoproterenol infusion.ResultsCompared with WKY rats, SHR rats had significantly higher blood pressure throughout the experimental period and at the end of 4‐week treatment the systolic blood pressure (SBP) was 212±9mmHg in SHR versus 122±15mmHg in WKY (P<0.001). Dantrolene treatment in SHR had no effect on blood pressure level (208±16 mmHg in dantrolene versus 212±9mmHg in vehicle, P>0.05). AF inducibility was not significantly different between WKY and SHR rats at baseline. However, under SS AF inducibility was significantly increased in SHR compared with WKY rats (58±28% in SHR versus 20±23% in WKY, P<0.01) and dantrolene treatment attenuated AF inducibility under SS in SHR (58±28% in SHR‐vehicle versus 27±21% in SHR‐dantrolene group, P<0.05). Dantrolene treatment also reduced AF duration (0.8±1.4s in dantrolene group versus 10.0±15.0s in vehicle group, P<0.05).Conclusions: Stabilizing RyR with dantrolene treatment did not affect hypertension development in SHR rats, indicating RyR dysfunction does not play an important role in mediating hypertension development in this animal model. SHR rats did not show increased AF inducibility compared with WKY rats at baseline; however, under SS, SHR rats had increased vulnerability to AF induction which was attenuated with dantrolene treatment, indicating that enhanced SS‐induced RyR dysfunction in SHR may be responsible for enhanced AF inducibility in hypertension.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Major discoveries on Spinal Cord Injury‐induced immune response
Authors: Jin Yining , Turley Alexandra E. , Kennedy Rebekah C. , Boss Allison P. , Liu Sheng , Lujan Heidi L. , Kumar Ramya K. , Watts Stephanie W. , Fink Greg D. , DiCarlo Stephen E. , Rockwell Cheryl E 
Published: June 2021

Cardiovascular disease (CVD) is a leading cause of death and morbidity for individuals with spinal cord injury (SCI). The risk for significant cardiovascular dysfunction is mediated, in part, by systemic low‐grade inflammation as well as abnormal and unstable autonomic control. Specifically, evidence documents a state of chronic inflammation in individuals with SCI. Understanding the mechanisms responsible for the inflammatory and immune responses to SCI has the potential to reduce the risk for CVD and positively impact the lives of millions of individuals and families living with SCI. To address this goal, we studied both paraplegic and tetraplegic rats to determine the effect of SCI on immune function. Splenic immune cells were collected from male Sprague Dawley paraplegic, thoracic2–3 (T2–3) and tetraplegic, cervical6–7 (C6–7) rats (16 weeks post‐transection). We found that SCI impacted both the adaptive and innate arms of the immune system. Evidence of adaptive immune impairment was shown through increased production of IgM and IgG antibodies by unstimulated B cells following spinal cord injury, most notably in the paraplegic group. We also observed a robust increase in IFNg production by activated T cells from tetraplegic and paraplegic animals. The increased production of IFNg (a Th1 cytokine) correlated with an increase in two other Th1 cytokines, TNFa and GM‐CSF. Although there was a modest increase in IL‐4 production by activated T cells from SCI rats, this did not correlate with other Th2 cytokines, such as IL‐5 and IL‐13. Overall, splenic T cells from SCI rats appear to be predisposed to a Th1‐like response. The innate immune system was shown to be modulated after SCI through an effect on NKT‐like cells. There was an increase in the percentage of NKT‐like cells (CD3+CD161+) in the SCI rats that was most prominent in the paraplegic group. Taken together, these data suggest that SCI results in alteration of innate and adaptive immune cell percentages and function, potentially impacting the immune and inflammatory responses following the injury to the spinal cord.Support or Funding InformationNHLBI HL070687 NIEHS ES024966 NHLBI HL122223This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Phasic, Rapidly‐Propagating Calcium Transients Occur in a Non‐Muscle Cell Network within the Mouse Urinary Bladder Wall
Authors: Tykocki Nathan R. , Hennig Grant W. , Koide Masayo , Wellman George C , Nelson Mark T. 
Published: June 2021

Multiple species, including humans, exhibit “non‐voiding” or “transient” contractions of the bladder wall during filling that are accompanied by large bursts of activity from bladder sensory nerves. This suggests that transient contractions play an important role as sensors of bladder fullness, but how transient contractions are generated remains unclear. Using genetically‐encoded Ca2+ indicator mice and novel macroscopic imaging techniques, we sought to determine what Ca2+ signals drive TC generation and coordination across the bladder wall. We utilized mice that constitutively express the Ca2+ indicators GCaMP5 or GCaMP6f as an expression‐dependent fate map of smooth muscle cells (Acta2 promoter) or non‐muscle cells (Trpv1 promoter) within the urinary bladder wall. We discovered that transient pressure events (TPEs) are actually the integration of numerous micro‐contractions of the bladder wall. These micromotions vary in position, frequency and duration, but result in regular, phasic increases in intravesical pressure. Ca2+ events in urinary bladder smooth muscle (UBSM) were restricted to small patches muscle cells and seemed to occur stochastically. Interestingly, we discovered a network of cells within the bladder wall of Trpv1‐GCaMP6f mice that were neither smooth muscle cells nor nerve fibers. This network exhibited extremely rapid and phasic Ca2+ transients that propagated quickly across the entire bladder wall, suggesting that the cells were electrically coupled. The slower waxing and waning of the high‐frequency Ca2+ transient intensity closely aligned with the frequency of TPEs. Surprisingly, this network of cells was unresponsive to the TRPV1 agonist capsaicin, suggesting that TRPV1 channels were no longer functional in these cells. These data suggest that the bladder wall micro‐motions underlying TPEs may be driven by phasic Ca2+ transients that occur in a non‐muscle cell network within the bladder wall.Support or Funding InformationSupported by NIH K01DK103840 (NRT) and R37DK053832 (MTN).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of heart rate variability biofeedback training on psychological state and cardiac autonomic regulation in stressed people
Authors: Arsac Véronique , Blons Estelle , Spiluttini Beatrice , Arsac Laurent M 
Published: June 2021

IntroductionPsychological stress is common in our fast‐paced society and strongly influences mental and physical well‐being. Specific training methods have been recently proposed to deal with the negative effects of stress. heart rate variability biofeedback training, a method whereby the subject controls an unusually breathing rate to reach cardiac coherence, has been shown to reduce anxiety and improve cardiac autonomic dynamics in diseased people as well as in young competitors. The present study was designed to examine the effects of short sessions of biofeedback (BFB) training in subjects classified as being severely stressed.MethodsTwenty‐four participants characterized by a high level of state anxiety, were randomly assigned into a BFB group (n=12) or a control Group (n=12). In the BFB group, cardiac coherence training using a biofeedback device (URGOfeel®, URGOTECH) was conducted during 5 weeks, 5‐min twice a day.Subjects completed two sessions of tests (before and after 5‐weeks BFB training). Each session consisted in 4 conditions, a baseline “quiet” condition, a condition of cognitive tasks (to assess different domains of executive functioning), and two conditions of cognitive tasks associated to two levels of environmental‐induced stress. To create gradual level of environmental stress, the experimental context was modified by generating visual and sound interferences with negative feedback and time pressure. Heartbeat intervals were recorded (Polar Belt) for 10‐min both at baseline and after 5‐weeks BFB training and was assessed in temporal domain (RMSSD) and from non‐linear analyses (entropy index calculated from MultiScale Entropy, MSE). Participants filled out a series of questionnaires on‐line, notably the Spielberger state anxiety questionnaire (STAI) and the NASA‐TLX to measure the impact of stress on anxiety and workload, before and after each session and conditions.ResultsBefore BFB training the induced stress, was associated with a high level of anxiety and a low entropy when compared to baseline and cognitive tasks conditions. After BFB training, both psychological state and entropy in cardiac dynamics were improved in every condition.Conclusionthe present study confirms the blunting of physiological complexity in heart rate dynamics in stressed subjects especially under acute stress. The phenomenon is generally associated with an altered heart‐brain interconnectivity and a lesser adaptive capacity to everchanging environments. The main outcome here was the efficiency of (very) short BFB training sessions to restore an improved autonomic control in stressed subjects whatever their environment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of the Menstrual Cycle on Hemoglobin Mass
Authors: Keller Melissa Faith , Lalande Sophie 
Published: June 2021

The impact of the menstrual cycle on oxygen‐carrying capacity remains equivocal. Previous studies reported either reductions or no significant changes in hemoglobin concentration during the follicular phase when compared to the luteal phase of the menstrual cycle. Changes in plasma volume associated with fluctuating estrogen and progesterone levels likely contribute to the variations in hemoglobin concentration observed throughout the menstrual cycle. Thus, measures of hemoglobin concentration do not accurately represent the oxygen‐carrying capacity of the blood. Hemoglobin mass represents a more direct measure of oxygen‐carrying capacity. However, the impact of menstrual blood loss on hemoglobin mass remains unknown. Therefore, the purpose of this study was to determine the effect of the menstrual cycle on hemoglobin mass in pre‐menopausal women. Twenty women (age: 23 ± 6 years, height: 167 ± 7 cm, weight: 66 ± 13 kg) with a regular menstrual cycle using (n = 9) and not using hormonal contraceptives participated in the study. Hemoglobin mass was assessed using the carbon monoxide rebreathing technique on three separate visits. Visits for women using hormonal contraceptives were scheduled in the early follicular phase (3–5 days post‐onset of menses), late follicular phase (14 days post‐onset of menses), and late luteal phase (10 days after the late follicular visit). Visits for women not using hormonal contraceptives were scheduled in the early follicular phase (3–5 days post‐onset of menses), late follicular phase (1–2 days post‐surge of luteinizing hormone in urine), and late luteal phase (10 days after the late follicular visit). While hemoglobin concentration was nearly significantly different across phases of the menstrual cycle (early follicular: 13.1 ± 1.2 g/dL, late follicular: 12.7 ± 0.8 g/dL, late luteal: 12.8 ± 0.9 g/dL, p = 0.08), hemoglobin mass did not significantly differ between menstrual cycle phases (early follicular: 615 ± 62 g, late follicular: 609 ± 66 g, late luteal: 606 ± 69 g, p = 0.90). Thus, menstrual blood loss has no significant impact on hemoglobin mass or oxygen‐carrying capacity in women with a regular menstrual cycle.Support or Funding InformationSmall Research Grant of the College of Education of the University of Texas at Austin.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Albuterol Improves Lung‐Emptying Dynamics in Patients with Cystic Fibrosis
Authors: Guo Winston , Baker Sarah E , Wiggins Chad C , Joyner Michael J , Dominelli Paolo B 
Published: June 2021

ObjectiveThe slope ratio (SR) is a metric that uses maximal expiratory flow‐volume (MEFV) curves to quantify lung‐emptying dynamics. SR values between 0.5–2.5 indicate homogeneous lung‐emptying, while values >2.5 are suggestive of heterogeneous lung‐emptying. Albuterol and exercise are commonly used to improve airflow in patients with cystic fibrosis (CF); however, the effects of these treatments on lung‐emptying dynamics are unknown. We hypothesized that SR values would decrease following albuterol and/or exercise, and that these decreases would be more pronounced following albuterol‐with‐exercise.MethodsNine patients (25±2 yrs, n=4 male, 5 female) diagnosed (genotype or sweat chloride) with CF underwent three interventions: i) albuterol (2.5 mg in 3 mL saline), ii) 30 mins of exercise (50% peak wattage), and iii) albuterol and exercise together. MEFV curves (spirometry) were obtained at 10 time points: immediately before (Pre) and 15 minutes after (T15) interventions. Forced expiratory volume in 1 second (FEV1) and forced expiratory flow for 25–75% (FEF25–75) of the forced vital capacity (FVC) were calculated for each curve. SR was calculated along the MEFV curve as the ratio between the tangent and chord slopes at serial volumes (200 mL increments), and SR values from 80%‐20% FVC were averaged to produce a single SR for each MEFV curve.ResultsCompared to exercise, albuterol and albuterol‐with‐exercise elicited greater increases in FEV1 (Pre: 3.00±0.26 vs 2.99±0.25 vs 3.06±0.23 L, p>0.05; T15: 3.00±0.27 vs 3.27±0.30 vs 3.34±0.28 L, p=0.03; exercise vs albuterol vs exercise‐with‐albuterol, for each comparison respectively), FEF25–75 (Pre: 2.52±0.40 vs 2.53±0.40 vs 2.57±0.36 L/s, p>0.05; T15: 2.48±0.39 vs 3.04±0.54 vs 3.10±0.43 L/s, p=0.04), and FVC (Pre: 4.19±0.38 vs 4.17±0.38 vs 4.22±0.37 L, p>0.05; T15: 4.16±0.39 vs 4.35±0.38 vs 4.40±0.41 L, p=0.02), as well as greater decreases in SR (Pre: 1.51±0.15 vs 1.56±0.12 vs 1.58±0.12, p>0.05; T15: 1.54±0.15 vs 1.46±0.17 vs 1.43±0.17, p=0.02). Changes in FEV1, FEF25–75, FVC, and SR were not different between albuterol and albuterol‐with‐exercise conditions (p>0.05). Reductions in SR were related to increases in FEV1 following interventions (r=−0.55, p<0.01).ConclusionsIn contrast to exercise, albuterol caused CF patients to exhibit greater increases in FEV1, FEF25–75, and FVC, along with greater decreases in SR. There was no additive effect of exercise on albuterol. Changes in FEV1 and SR were inversely correlated. These data suggest that albuterol promotes bronchodilation and homogeneous lung‐emptying in CF patients, and that the SR metric is effective for assessing patterns of bronchodilation following administration of different bronchodilators.Support or Funding InformationSupported by HL131151 (SEB) and Mayo Clinic Internal FundingThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Quantifying Maximal Oxygen Uptake using Lean Body Mass in Children with Obesity
Authors: Bhammar Dharini M , Marines‐Price Rubria , Wilhite Daniel P , Bernhardt Vipa , Adams‐Huet Beverley , Gupta Olga , Martinez‐Fernandez Tanya , Babb Tony G 
Published: June 2021

IntroductionThe purpose of this study was to examine whether maximal oxygen uptake (V̇O2max) prediction equations based on lean body mass can overcome the confounding effect of fat mass on quantification of cardiorespiratory fitness in children with obesity.MethodsForty‐nine children (23 with obesity; BMI ≥ 95th percentile) completed a dual‐energy x‐ray absorptiometry scan for estimating body composition and incremental maximal and verification exercise tests till volitional exhaustion for estimating V̇O2max. Prediction equations based on lean body mass (LBM) and body mass from Cooper D.M. et al 2016 were used to predict V̇O2max [Boys: (0.059 × LBM) − 0.103; (0.052 × body mass) − 0.266. Girls: (0.055 × LBM)–0.187; (0.037 × body mass) + 0.022].ResultsIn children without obesity, predicted V̇O2max based on body mass was 100 ± 10mL/min higher than predicted V̇O2max based on LBM (P < 0.001). In children with obesity, predicted V̇O2max based on body mass was 906 ± 33mL/min higher than predicted V̇O2max based on LBM (P < 0.001). Predicted V̇O2max based on body mass was more strongly associated with fat mass (r = 0.81) compared with predicted V̇O2max based on LBM (r = 0.51); P<0.001. The V̇O2max vs. LBM slope was similar for children with (0.040 L·min−1·kg−1) and without obesity (0.043 L·min−1·kg−1). Percent predicted V̇O2max based on LBM was 13% lower in children with obesity compared with children without obesity (P < 0.001). Percent predicted V̇O2max based on body mass was 37% lower in children with obesity compared with children without obesity (P < 0.001).ConclusionsReferencing V̇O2max to body mass substantially underestimates cardiorespiratory fitness in children with obesity due to the confounding effect of metabolically inactive fat mass. It would be prudent to measure LBM and reference V̇O2max to LBM for a less biased estimation of cardiorespiratory fitness in children with obesity.Support or Funding InformationThis research was supported by NIH R01 HL136643, Texas Health Presbyterian Hospital Dallas, King Charitable Foundation Trust, and unrestricted funds from Dr. Pepper Snapple.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.