bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transport and Metabolism of Adenosine and its Metabolites in Capillary Endothelial Cells of Guinea Pig Hearts
Authors: Liu Aiping , Bassingthwaighte James B. 
Published: June 2021

Adenosine (Ado) plays an important role in cardioprotection during ischemia by enhancing coronary flow through binding to purinoceptors on smooth muscle cells (SMC), and by preserving nucleotide pools through purine salvage in cardiomyocytes (MC). However, two questions impede our understanding of the mechanism by which Ado acts on MCs or SMCs: (1) how much Ado reaches cardiomyoctyes or SMC when EC avidly take‐up Ado from blood stream and interstitium? and (2) how much Ado degrades to uric acid (UA), or is salvaged back into cellular pools, mainly ATP? Our goal here is to quantify the fluxes of Ado and its metabolites in ECs. The multiple‐indicator‐dilution technique (MID) was used to measure the capillary transport and metabolism of Ado and metabolites in isolated, Krebs‐Ringer perfusated guinea pig hearts. Radiolabeled [14C]‐ adenosine, or inosine, or hypoxanthine, or xanthine was injected with [131I]‐albumin (intravascular reference solute) and [3H] AraH or L‐[3H] glucose (extracellular references) as a bolus into the coronary flow; venous outflow dilution curves of the injectate and its metabolites were quantified with HPLC and LS counting. The permeabilities of each solute (via interendothelial clefts, PSg, trans‐endothelial membrane, PSecl, trans‐cardiomyocytes PSpc) and the metabolism in ECs and MCs were estimated by fitting the MID curves with a general convection‐diffusion‐exchange‐reaction model, Gentex. Results are: Intracellular sequestration of injected Ado is high compared to its metabolites (~60% of Ado vs. ~50% of Ino). Similarly, PSecl is higher for Ado than metabolites, INo>Hx>Xa> UA (Ado:1.9±0.7 vs. Ino:1.7±0.5 vs. Hx: 0.5±0.1 ml·min−1·g−1). The low permeabilities help to retain purine in the cells. Plasma injectate Ado that enters ECs is estimated to be ~50% oxidized to UA, ~50% retained; Hx is ~67% oxidized, ~23% retained, both presumably incorporated into nucleotide pools. Thus ECs actively participate in purine salvage via both Ado and Hx. Uncertainty for EC parameters is much smaller than for MC. Having well‐defined parameters for permeabilities and metabolism for Ado and its metabolites in ECs is an essential step toward understanding the fate of endogenous Ado generated from cardiomyocytes during ischemia and reperfusion.Support or Funding InformationOur study was supported by NIH research grant U01HL122199.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RESVERATROL IMPROVES MICROVASCULAR FUNCTION IN ADULTS WHO REPORTED ADVERSE CHILDHOOD EVENTS
Authors: Miguelez Paula Rodriguez , Looney Jacob , Thomas Jeffrey , Pollock Jennifer , Harris Ryan 
Published: June 2021

INTRODUCTIONAdversity early in life, referred to as adverse childhood events (ACEs), has been associated with the development of cardiovascular disease (CVDs) during adulthood. Microvascular dysfunction plays a pivotal role in the etiology of CVDs through a reduction in nitric oxide (NO)‐dependent vasodilation. Lower concentrations of sirtuin 1 (Sirt1), an NAD‐dependent protein that increases NO metabolism, have been described in multiple CVDs.PURPOSEThis study sought to test the hypothesis that an acute dose of resveratrol (RES), a natural activator of Sirt1, will improve MVF in adults who reported ACEs.METHODSTen adults (34 ± 3 yrs), with no evidence of overt CVD, participated in the study. Based on the ACE questionnaire, all participants had self‐reported an ACE score of 4 or greater. Two protocols were used to evaluate MVF using Laser Doppler flowmetry: 1) local thermal hyperemia (LTH), with a maximal plateau phase primarily mediated by NO, and 2) post‐occlusive reactive hyperemia (PORH), partly dependent on NO metabolism. MVF assessments were determined before and 90 min after an acute dose of either RES (500 mg) or Placebo (P), separated by at least 7 days and are expressed as cutaneous vascular conductance (CVC; cutaneous flux/mean arterial blood pressure). Maximal dilation capacity was evaluated through LTH. Skin resistance was also calculated for every individual and every treatment using Ohm's law and considered in all the statistical analysis.RESULTSNo differences in resting CVC were observed between days (0.11 ± 0.08 vs. 0.11 ± 0.03 PU/mm Hg; p=0.297) or with the change from either treatment (ΔRES: −0.03 ± 0.03 vs. ΔP: −0.01 ± 0.01 PU/mm Hg; p=0.653). In addition, resveratrol significantly (p=0.005) increased max LTH when compared with P (ΔRES: 0.12 ± 0.24 vs. ΔP: −0.06 ± 0.26, PU/mm Hg). Moreover, RES significantly (p≤0.001) prevented the decrease in PORH relative to the maximal dilation capacity when compared with placebo (ΔRES: −6.4 ± 1.4 vs. ΔP: −18.1 ± 17.8 %CVC max). In addition, the acute dose of RES increased concentrations of Sirt1 (RES: 1.3 ± 0.1 vs. ΔP: −0.4 ± 0.3 ng/ml; p=0.075) which was significantly associated with the max LTH response (r=0.760; p=0.011).CONCLUSIONThese findings document an improvement in MVF after an acute oral dose of resveratrol in adults who have reported ACEs. Future studies are warranted to investigate the long term effects of resveratrol on MVF in adults who have reported ACEs.Support or Funding InformationSupported in part by NIH/NHLBI P01HL069999 (JSP, RAH) and 16POST31080031 (PRM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cerebrovascular Reactivity in Obstructive Sleep Apnea: Impact of Physical Activity
Authors: Sauder Christina J. , Carter Katrina J. , Ward Aaron T. , Morgan Barbara J. , Hagen Erika W. , Peppard Paul , Schrage William G. 
Published: June 2021

BackgroundObstructive sleep apnea (OSA) is associated with increased risk of cerebrovascular disease and stroke. This risk may be partially due to reduced cerebrovascular function. Conversely, regular physical activity (PA) reduces the risk for cerebrovascular disease. Whether PA levels can predict the OSA‐related reductions in cerebrovascular function remains unknown. Therefore, we tested the hypothesis that the level of PA alters the relationship between OSA‐severity and cerebrovascular dysfunction.Methods245 healthy adults (113 females; mean age ~60 years; smoking, continuous positive airway pressure (CPAP) treatment, and diabetes were exclusionary) performed overnight polysomnography to determine the presence and severity of OSA. Next, cerebrovascular function was tested in the middle cerebral artery (MCA) in response to CO2 rebreathing (10 mmHg increase), expressed as cerebrovascular reactivity (CVR; cm/sec/mmHg PETCO2). PA was estimated using the Paffenbarger Physical Activity Questionnaire and expressed as Metabolic Equivalent (MET) hours per week. Data were analyzed by linear regression analysis using CVR as the outcome variable and mean nighttime arterial oxygen saturation (SaO2) as the main independent variable. Model adjustments included age, sex, number of metabolic syndrome factors, number of caffeinated beverages per day, and mean arterial pressure (MAP) slope response to CO2. We also included a model that had an additional adjustment for PA.ResultsIn an unadjusted model, higher nighttime SaO2 was a predictor of higher CVR (p < 0.05). When adjusted with the aforementioned variables, both SaO2 and MAP slope were predictors of CVR. Adding PA to the adjusted model did not change the overall relationship between SaO2 and CVR.ConclusionsThese data fail to demonstrate that PA level has a substantial impact on CVR in subjects with OSA.Support or Funding InformationR01HL062252, R01HL075035, and UL1RR025011This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The role of adiponectin in exercise training‐induced vascular adaptation
Authors: Sepulveda Jaime Luis , Ghosh Payal , Delp Michael , Pritchard Emily , Maraj Joshua , Wahl Jake , Restrepo Alexis , Morgan Hannah , Ulrich Brody , Abeln Clayton , Nolan Jacob , Kenney Mary , Patterson Nicolas , Rosenthal Shaianne , Vega‐Figueroa Leilanie , Sadowsky Dylan , McKinley‐Caspanello Carly , Schwartz Kaley , Muller‐Delp Judy 
Published: June 2021

We have previously reported that in old rats, reversal of age‐related vascular dysfunction by exercise training correlates with an increase in circulating adiponectin and its signaling within coronary vascular smooth muscle. In the current study, we investigated the effect of deletion of adiponectin on exercise training‐induced vascular adiponectin. C57BL/6 wild‐type (WT) or homozygous adiponectin knockout (AdipoKO) mice were obtained at 10–12 wks of age and underwent treadmill exercise training (EX) (12 m/min, 5° incline, 1 hr/day, 5 days/wk for 8 wks) or remained sedentary (SED) in cages. Arterioles isolated from cardiac and soleus muscle were assessed for contractile and vasodilatory function, and capillarity of the soleus muscle was evaluated. Exercise training increased flow‐induced dilation significantly in coronary arterioles of WT mice (P<0.01 EX vs. SED), but decreased flow‐induced dilation in coronary arterioles from AdipoKO mice. ACh‐induced dilation was reduced in coronary arterioles from AdipoKO mice as compared to those from WT mice (P<0.05 AdipoKO vs. WT). Exercise training reduced ACh‐induced dilation in arterioles from WT mice, but increased ACh‐induced dilation in arterioles from AdipoKO mice. Baseline capillarity increased in the soleus muscle of AdipoKO mice as compared to WT mice, but an exercise training‐induced increase in capillarity, detected in WT mice, was absent in AdipoKO mice. Contractile responsiveness to phenylephrine was increased in arterioles from the soleus muscle of both WT and AdipoKO mice (P<0.01 EX vs. SED in both WT and AdipoKO). These data indicate that adiponectin is a critical contributor to exercise training‐induced vascular adaptations; however, locally produced adiponectin may be more critical than circulating adiponectin in mediating these adaptations.Support or Funding InformationFlorida State University College of MedicineThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Early Exercise Training Postpones Hypertension Progression via Activation of Central ACE2‐Ang(1–7)‐Mas Axis in Prehypertensive Rats
Authors: Pan YanXia , Peng WenWen , Zhao XiaoLin , Gao Lie , Lin Cheng , Cheng XiuYun 
Published: June 2021

ObjectivesTo investigate the effects of exercise training on the development of hypertension in spontaneously hypertensive rats (SHR) and explore the underlying mechanisms by focusing on the central ACE2‐Ang (1–7)‐MAS axis.MethodsThe male SHR (n=20, 5 weeks old) and 20 normotensive Wistar Kyoto rats (WKY) were randomly assigned to sedentary (Sed) group or exercise training (ExT) group. The trained rats run on a treadmill in 20 m/min, 30 min/day, 5 day/week for 20 weeks. Systolic blood pressure (SBP) were measured by a tail‐cuff method. The baroreflex sensitivity (BRS) was assessed by intravenous injection of phenylephrine under anesthesia. The expression of ACE2 and MAS receptors mRNA and protein in the cardiovascular centers was determined by real‐time PCR and Western blot. Alterations in the BRS were evaluated before and after intracerebroventricular injection of MAS receptor agonist Ang (1–7) and its antagonist A779, respectively.Results(1) Exercise training significantly postponed the development of hypertension in SHR and decreased SBP in both SHR and WKY as compared with Sed groups (P<0.01 and P<0.05). (2) Exercise training enhanced blood pressure regulation and improved the BRS in the SHR (P<0.01). (3) The expression of ACE2 and MAS receptor mRNA and protein in rostral ventrolateral medulla (RVLM), nucleus tract solitarius (NTS), and paraventricular nucleus (PVN) was up‐regulated in SHR+ExT group (P<0.05, P<0.01). (4) Central administration of A779 abolished the benefits of exercise‐induced improvement of BRS in the SHR+ExT rats (P<0.01). In contrast, Ang (1–7) improved the BRS in both SHR+Sed group and SHR +ExT group (P<0.05).ConclusionExercise training postpones hypertension progression and improves blood pressure regulation, which is associated with the enhancement of central ACE2‐Ang(1–7)‐Mas axis.Support or Funding InformationNational Natural Science Foundation of China (No. 81372111) and Natural Science Foundation of Fujian Province of China (No. 2014J01339)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deciphering the Neural Signature of Human Blood Pressure Control
Authors: Manuel Jorge , Nazarenko Nataliia , Heusser Karsten , Tank Jens , Jordan Jens , Beissner Florian 
Published: June 2021

The aim of this study was to measure the activity of hypothalamic and brainstem centers regulating blood pressure in humansThe human body has several systems to regulate blood pressure, one of which is the baroreflex. It is mediated by a number of nuclei in the brainstem and hypothalamus that via autonomic efferents adjust the mean arterial pressure by altering both the force and speed of the heart's contractions, as well as systemic vascular resistance. While cortical centers influencing the baroreflex have been studied in humans using functional magnetic resonance imaging (fMRI), the brainstem region suffers from strong physiological noise that makes detection more difficult. Here, we combined high‐resolution fMRI with lower body negative pressure (LBNP) and concomitant autonomic recordings hypothesizing that such an approach would make it possible to detect hypothalamic and brainstem nuclei controlling the baroreflex in humans.15 healthy subjects were scanned using a 3T MR scanner. The protocol involved SMS‐EPI functional scans (voxel size=2×2×2 mm3) as well as T1‐weighted structural scans (voxel size=1*1*1.2 mm3). LBNP stimulation was delivered using a custom‐made MR‐compatible pressure chamber and a vacuum cleaner that was controlled by a digital pressure gauge. FMRI data were minimally preprocessed using tools from FMRIB Software Library (FSL v5.0) including motion correction, unwarping, temporal high‐pass filtering and normalization to a study template. The data were masked to retain only the brainstem and hypothalamus, excluding the adjacent areas with high physiological noise. Statistical analysis was conducted using masked independent component analysis (mICA), spectral analysis, and network modelling.We found activations related to the LBNP paradigm in multiple nuclei known to be involved in baroreflex regulation. These included the nucleus of the solitary tract and the caudal ventrolateral medulla in the lower brainstem as well as the paraventricular hypothalamic nucleus and lateral hypothalamus. We further observed significant activity changes on the lower ventral medullary surface. Frequency analysis revealed that the BOLD signal in the rostroventrolateral medulla showed spectral changes in the Mayer band (0.1 ± 0.035 Hz) during LBNP.Being able to measure baroreflex nuclei in vivo is an important step towards the understanding of this system in humans. Our results show the importance of selected nuclei in the hypothalamus and brainstem.Support or Funding InformationFunding: Horst Goertz FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MRI Characterization of Age‐Associated Changes to the Cerebral Arteries in a Rodent Model of Aging and Hypertension
Authors: McPherson Rebecca L. , Naraine Akshay , Lee Diana , Rejimon Abinand , Fishbein Kenneth W. , Spencer Richard G. , Lakatta Edward G. , Fedorova Olga V. 
Published: June 2021

Cerebral blood vessel remodeling occurs in response to aging and hypertension. Of importance are structural changes that occur to the circle of Willis and the impact of these changes on blood flow within the brain, especially in regions associated with learning and memory, such as the hippocampus. In the present study, we apply MRI to a rodent model of aging and hypertension to elucidate changes in the circle of Willis during aging and age‐associated hypertension.HypothesisWe hypothesized that arteries comprising the circle of Willis in hypertensive Dahl‐salt sensitive rats (Dahl‐S) will exhibit age‐related volume changes, these changes will impact metabolite levels in the hippocampus and the effects will differ between Dahl‐S and age‐matched Sprague‐Dawley rats (SD).MethodsWhole brain time‐of‐flight (TOF) 3D MRI and MRS (spectroscopy) of the hippocampus were acquired using a 7 Tesla 30 cm Bruker Biospec scanner in SD and Dahl‐S male rats on normal 0.5% NaCl intake at 3, 6 and 12‐mo of age (n=5/group). Cerebral arteries comprising the circle of Willis (cerebral arterial circle (CAC), caudal communicating artery (CCA) and rostral communicating artery (RCA)) were manually segmented using AMIRA. MRS data were processed using LCmodel. Systolic blood pressure (SBP) was measured via the tail‐cuff method at each time point before MRI scans. Data were analyzed using 2‐way ANOVA followed by a Tukey's posthoc test, and are presented as mean ± standard deviationResultsAt 3‐mo, SBP did not differ between Dahl‐S vs SD (134.6±14.1 vs 131.4±8.8 mmHg). However, Dahl‐S had higher SBP vs SD at 6‐mo (165.8±20.6 vs 123.7±8.8 mmHg) and 12‐mo (166.1±16.9 vs 142.2±12.8 mmHg). The CAC volume was greater in SD vs Dahl‐S at 3 and 12‐mo but did not differ at 6‐mo (Table). Importantly, the CAC was not visible by MRI in Dahl‐S at 12‐mo of age, except in one animal. The CCA volume was greater in SD vs Dahl‐S at 12‐mo and did not differ at 3 or 6‐mo. The RCA volume did not differ between strains at any time point. No arterial volume differed with age in SD. In Dahl‐S, the CCA and RCA volumes were larger at 6‐mo compared to 3 and 12‐mo (Table). Total N‐acetylaspartate (NAA) in the hippocampus was lowest at 6‐mo in both strains, compared to 3 and 12‐mo, but did not differ between strains at any time point (Table).ConclusionWe observed variations with strain and age in the volume of arteries in the circle of Willis in normotensive SD and hypertensive Dahl‐S. Hypertensive Dahl‐S at 6‐mo of age may experience increased metabolic demand and blood volume requirements in the brain.Support or Funding InformationThis work was supported solely by the NIH/NIA Intramural Research Program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Rapamycin Alters MicroRNA Signature Profile in Diabetic Rabbit following Myocardial Ischemia Reperfusion Injury: A Preclinical Approach for Cardioprotection.
Authors: Samidurai Arun , Ockaili Ramzi , Roh Sean K. , Kukreja Rakesh C. , Das Anindita 
Published: June 2021

BackgroundMyocardial ischemia reperfusion (I/R) injury associated with cardiovascular risk factors and comorbidities, including Diabetes (DM), is a major complication for development of heart failure. Mammalian target of Rapamycin (mTOR) is robustly active in DM and further exacerbated during I/R. mTOR inhibition with rapamycin at reperfusion preserves cardiac function with reduction of myocardial infarction in diabetic mice. Recent advances in non‐coding RNA analysis demonstrates microRNA (miR) plays an important role in cardiovascular diseases. We examined the effect of rapamycin treatment at the onset of reperfusion in a conscious diabetic rabbit model of I/R and identified differentially regulated miRs.Methods and ResultsTo induce diabetes, alloxan monohydrate (125 mg/kg, i.v.) was administered in New Zealand male rabbits (n=26; average 3 kg, 4 month old). Blood glucose levels increased to 345±66 mg/dL (n=10) following 2 weeks of alloxan administration. The animals were categorized to three groups: Diabetes (DM), Diabetes subjected to I/R (DM+I/R) and Diabetes underwent I/R and treated with Rapamycin (DM+I/R+Rapa). Post 7 days of implantation of balloon occluders on the top of the coronary artery, the conscious rabbits were subjected to 45‐min ischemia and 3 days of reperfusion by inflating/deflating the balloon. Rapamycin (0.25 mg/kg, i.v.) or DMSO (vehicle) was infused 5 min before reperfusion. Plasma was collected at baseline, 1, 2, 4 and 24 hours during the reperfusion and cardiac Troponin I (cTnI) release was measured by ELISA. The results show that rapamycin significantly reduced myocardial infarction in DM rabbits following I/R (Figure A) as assessed by triphenyltetrazolium chloride staining. Rapamycin also reduced cTnI at 1 hr and 2 hr of reperfusion as compared to vehicle alone (Figure B). RNA isolated from risk area of left ventricle heart tissue from different groups (n=3) was subjected to miRNA‐Array analysis using μParaflo® Microfluidic Biochip Technology (Figure C). The results show 34 out of 761 miRs were differentially regulated with Rapamycin treatment (p<0.01) (Figure D). Enrichment Analysis and Annotation of selected miRs were performed using miEAA and DAVID tools to identify potential targets and its interaction with mTOR signaling pathway.ConclusionThis Preclinical translational study demonstrates that rapamycin could be a promising drug in attenuation of reperfusion injury in diabetic patients following acute MI by altering novel miRs.Support or Funding InformationNIH RO1HL134366 (AD & RCK) & CCTR Endowment Fund UL1RR031990 (AD)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Fat Fed Nr4a1 Knock Out Mouse has Significant Modulation of Mitochondrial Respiration Across Various Tissues
Authors: Wynn Adam G. , Garland Kevin G. , Kener Kyle B. , Weber K. Scott , Bikman Benjamin T. , Hancock Chad R. , Tessem Jeffery Sivert 
Published: June 2021

The orphan nuclear receptor Nr4a1 is critical for fuel utilization in various tissues. Studies have shown that Nr4a1 controls expression of genes necessary for mitochondrial respiration. Further studies have demonstrated that Nr4a1 knock out animals fed a high fat diet have significant shifts in fuel utilization profiles. We sought to define the changes in mitochondrial respiration and function across various tissues in wild type and Nr4a1 KO mice fed a normal chow or high fat chow diet for twenty weeks. Nr4a1 KO mice fed the high fat diet had significantly worse glucose tolerance than wild type animals fed the high fat diet. Furthermore, Nr4a1 deficient animals demonstrated significant changes in the macrophage population as compared to wild type animals. Mitochondrial respiration of muscle and liver from Nr4a1 KO animals fed normal chow or high fat diet were significantly impaired compared to the wild type controls. Interestingly, mitochondrial respiration from macrophages was significantly enhanced in the Nr4a1 KO animals. These data demonstrate systemic effects of Nr4a1 deletion, as well as demonstrating a mechanism by which Nr4a1 KO have shifts in fuel utilization during high fat feeding regimes.Support or Funding InformationThis study was funded by a BYU ORCA Grant to KG and a BYU MEG Grant to JST.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.