bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbonic Anhydrase Inhibition: Effect on Rat Hearts In Vitro With and Without pH Perturbations
Authors: Wasinger Nicholas A. , Geisbuhler Timothy P. , Brechue William F. 
Published: June 2021

Myocardial force generation is modulated by stretch‐induced mechanisms. The Starling effect relates to increased force following stretch due to venous return. The Anrep effect is a change in contractility with stretch secondary to increased afterload. Both mechanisms are related to intracellular Ca2+ dynamics. Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide (CO2) which is involved in cellular acid‐base balance. In skeletal muscle in vitro, inhibition of CA leads to increased fatigue due to altered Ca2+ handling at the sarcoplasmic reticulum. Our purpose was to investigate the role of CA in stretch‐induced change in myocardial force generation.MethodsHearts from Sprague‐Dawley rats were perfused in the working Langendorff style with Krebs‐Henseleit buffer [pH +/− 7.35 or 6.20, supplemented with 0.2 to 0.8% serum albumin (BSA)] and allowed to equilibrate 5 min under baseline preload (10 mmHg) and afterload (55 mmHg) conditions. Performance was examined at preloads of 10, 15, and 20 mmHg and constant afterload (55 mmHg); preload was then returned to 10 mmHg, and performance examined at afterloads of 55, 60, and 65 mmHg with constant preload (10 mmHg). Ethoxzolamide (Eth, 0.1 μM) or vehicle (water) was added to the perfusing buffer and the preload/afterload protocol repeated after 5 min equilibration with treatment. Systolic and diastolic pressure, heart rate, and dP/dt were monitored during the protocol. Performance was evaluated for individual parameters as a ratio of (value post‐addition)/(value pre‐addition) (hereafter called Ppost/Ppre).ResultsColloids in the perfusing medium preserve cardiac performance by preventing tissue edema. Cardiac performance (that is, the ability of the heart to maintain output and pressure) was best preserved over 40 min using BSA=0.8% (w/v). Dropping the pH to 6.2 from 7.35 increased Ppost/Ppre with regard to mean systolic pressure [1.04 ± 0.14 at 6.2 vs 0.47 ± 0.48 at 7.35 (p <0.05)], decreased Ppost/Ppre for peak systolic pressure [0.97 ± 0.02 at 6.2 vs 1.05 ± 0.03 at 7.35 (p <0.05)], and decreased Ppost/Ppre for minimum diastolic pressure [1.07 ± 0.01 at 6.2 vs 1.18 ± 0.06 at 7.35 (p <0.05)]. Addition of Eth decreased Ppost/Ppre for peak systolic pressure [1.00 ± 0.02 at 7.35 with Eth vs 0.89 ± 0.05 at 7.35 without Eth (p <0.05)] and increased Ppost/Ppre for minimum diastolic pressure [1.03 ± 0.05 at 7.35 with Eth vs 1.18 ± 0.06 at 7.35 without Eth (p <0.05)] at pH=7.35. Addition of Eth neither increased nor decreased Ppost/Ppre for any performance parameter examined at pH=6.20.ConclusionCA inhibition may lead to correction of function disrupted by pH perturbation.This 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 PI3‐kinase in Angiotensin II‐induced Cardiac Hypertrophy: Shift from Class III to Class I
Authors: Zhong Tiecheng , Guo Lirong , O'Rourke Stephen T. , Sun Chengwen 
Published: June 2021

Cardiac hypertrophy is initially an adaptive response to increased hemodynamic workload or defective contractile machinery; however, in the long‐term, it contributes to heart failure and sudden cardiac death. The extracellular regulatory factors and intracellular signaling pathways involved are not fully clear. Here, we studied the chronic effect of Ang II infusion on cardiac hypertrophy and fibrosis, and evaluated the role of class I PI3‐kinase in these actions of Ang II using lentiviral vector‐mediated expression of a dominant negative form of Class I PI3‐kinase subunit p85α in the heart of rats. Subcutaneous 4‐week infusion of Ang II induced severe cardiac hypertrophy and perivascular fibrosis in the heart. Cardiac transduction of Lv‐DNp85 abolished Ang II‐induced phosphorylation of Akt in the heart, as well as Ang II‐induced cardiac hypertrophy and perivascular fibrosis. Next, we examined intracellular mechanisms underlying Ang II‐induced cardiac hypertrophy in cultured cardiomyocytes. It is well known that mitochondrial oxidative stress mediates Ang II‐induced cardiac hypertrophy and the major source of reactive oxygen species (ROS), damaged mitochondria, is cleared by autophagy (also called mitophagy) in cardiac myocytes. Treatment of cardiomyocytes with Ang II (10−9 to 10−5 M) significantly increased autophagy with two phases (increases at low doses, decreases at high doses, peaked at 10−7 M). Ang II (10−6 M)‐induced increases in autophagy were significantly potentiated by PI3‐kinase Class I inhibitor, LY294002 (1 μM) and dramatically attenuated by 3‐Methyladenine (3‐MA, 1 μM), a PI3‐kinase Class III inhibitor. Ang II‐induced mitochondrial ROS production, measured using MitoSOX, was attenuated by LY294002 and potentiated by 3‐MA significantly. PI3‐kinases activity were measured using ELISA in cardiomyocytes, demonstrating that Ang II (10−6 M, i.e. high dose) significantly increased the activity of both Class I and Class III PI3‐kinases; however, Ang II (10−9 M, i.e. low dose) selectively elevated PI3‐kinase Class III activity. Together these data suggest that Ang II could have dual effects in the heart: 1) a protective arm to prevent ROS over‐generation in physiological cardiac hypertrophy, which is mediated by a Class III PI3‐kinase/autophagy‐dependent pathway; and 2) a deleterious arm due to increased mitochondrial ROS production through inhibition of autophagy by a Class I PI3‐kinase pathway in cardiomyocytes.Support or Funding InformationSupported by NIH NS55008.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Flow Mediates Collecting Duct Histone Deacetylase 1 Nuclear Export
Authors: Sedaka Randee S. , Hyndman Kelly A. , Pollock Jennifer S. 
Published: June 2021

Urinary flow within the renal tubules, especially the inner‐medullary collecting duct (IMCD), increases after high sodium consumption. We previously reported that this natriuretic response is due, in part, to elevated nitric oxide (NO) production without associated changes in NO synthase (NOS) expression. This suggests that high flow increases NO production via increased NOS activity. Histone deacetylase 1 (HDAC1) has recently been cited as a flow‐responsive protein and may post‐translationally deacetylate lysines on non‐histone proteins. Therefore, we hypothesized that flow‐mediated increases in NO production occur via HDAC1. Mouse IMCD cells were grown to confluency on glass slides, then placed under static conditions or 10 dynes/cm2 fluid‐flow for 1 hour at 37°C in the presence of vehicle (0.1% DMSO) or MS‐275 (300 nM), HDAC1‐selective inhibitor. Nitrite production, analyzed by HPLC, increased in response to flow >5‐fold (static: 231.4±31.1, flow: 1291.49.2±183.8 pmol/mg pr/hr; n=7/group, p<0.0001). MS‐275 significantly decreased NO production in response to flow (MS‐275: 342.8±44.0 pmol/mg pr/hr; n=9/group, p<0.0001). HDAC1 expression (static: 1.00±0.2, flow: 0.98±0.1 RDU/β‐actin; n=6/group, p>0.05) and activity (static: 1.00±0.06, flow: 0.85±0.02 RDU/β‐actin; n=3/group, p>0.05) was unchanged with flow in whole cell lysate. However, HDAC1 immunofluorescent staining of post‐flow IMCD cells suggested the presence of both nuclear and cytosolic HDAC1 and nuclear extraction of these flowed samples revealed a significant decrease in nuclear HDAC1 expression (static: 1.00±0.1, flow: 0.68±0.1 RDU; n=6/group, p<0.05), indicating nuclear export. Calcium, a key player in classical NOS activation, has also been reported to activate HDAC nuclear export. Thus, we further hypothesized that flow activation of NO production as well as flow‐mediated export of HDAC1 is calcium‐dependent. Flow‐induced NO production was abolished in the absence of calcium (flow+vehicle: 2038.1±402.0; flow+BAPTA: 377.7±75.3 pmol/mg pr/hr; flow+calcium‐free media: 474.8±133.2 pmol/mg pr/hr; n= 5–11/group, p<0.001). However, flow mediated nuclear HDAC1 export was similar in the presence and absence of BAPTA treatment (flow: 0.75±0.04, flow+BAPTA: 0.74±0.03 RDU; n=6/group, p>0.05). In conclusion, IMCD NO production in response to flow is both calcium‐ and HDAC1‐dependent, but extracellular calcium appears not to facilitate the flow‐mediated nuclear export of HDAC1. Further studies will elucidate the disparate mechanism(s) of flow‐mediated HDAC1‐dependent NO production from flow‐mediated HDAC1 nuclear export.Support or Funding InformationThis work was supported by funding from the National Institutes of Health ‐ P01 HL136267 to Dr. Jennifer Pollock and F31 DK111067 to Randee Sedaka.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Oxidative Stress During Simulated Hemorrhage Elicited by Lower Body Negative Pressure
Authors: Park Flora S. , Kay Victoria L. , Anderson Garen K. , Sprick Justin D. , Rickards Caroline A. 
Published: June 2021

BackgroundHemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Hemorrhage also elicits an oxidative stress response as a direct result of losing blood volume, or as an indirect response to ischemia‐reperfusion injury. Lower body negative pressure (LBNP) is a well validated, non‐invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of LBNP.Methods15 healthy human subjects (11M, 4F; 27 ± 1 y) were recruited for a step‐wise LBNP exposure to presyncope (systolic blood pressure <80 mmHg or subjective presyncopal symptoms). After baseline, LBNP pressure progressively decreased every 5 minutes to −15, −30, −45, −60, −70, −80, −90, and −100 mmHg. Arterial pressure and stroke volume were measured continuously via finger photoplethysmography, and venous blood samples were collected at baseline and during the LBNP profile. Plasma samples were analyzed for F2‐isoprostanes, a global marker of oxidative stress, via gas chromatography/mass spectrometry.ResultsThe magnitude of central hypovolemia, indexed by the % change in stroke volume, ranged from a 27% to 74%. LBNP induced a −12.6 ± 2.6 % decrease in MAP (%Δ MAP) from baseline (P<0.001). F2‐isporostanes increased by 28.5 ± 11.6 % (P=0.05) from baseline (24 ± 2 pg/ml) to presyncope (29 ± 3 pg/ml). The increase in F2‐isoprostanes was not associated with the decrease in MAP (r=0.05).ConclusionSimulated hemorrhage elicited by step‐wise LBNP to presyncope elicited an increase in a global marker of oxidative stress. These findings have important implications in the study of hemorrhage and potential application of targeted interventions.Support or Funding InformationFunding Source: Owens Foundation Grant and UNTHSC ICMD Junior Faculty Seed Grant.Analysis of eicosanoids (F2‐isoprostanes) were performed in the Vanderbilt University Eicosanoid Core Laboratory.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Arginine Vasopressin Infusion In C57BL/6J Mice Induces Changes In The Placenta Transcriptome That Parallel Changes Observed In Placenta From Human Preeclampsia
Authors: Deng Guorui , Sandgren Jeremy A. , Keen Henry L. , Perschbacher Katherine J. , Zhang Shao Y. , Santillan Donna A. , Pierce Gary L. , Gibson‐Corley Katherine N. , Santillan Mark K. , Sigmund Curt D. , Grobe Justin L. 
Published: June 2021

Preeclampsia (PE), a cardiovascular disorder of late pregnancy characterized by new onset hypertension and proteinuria, remains a devastating disease affecting approximately 10% of all pregnancies in the United States. Multiple independent studies demonstrate a correlation between PE and elevated maternal plasma copeptin, the C‐terminal fragment of arginine vasopressin (AVP), which supports the concept that AVP secretion is elevated during PE. Previously we demonstrated the sufficiency of chronic low‐dose AVP infusion to initiate major phenotypes of PE in pregnant C57BL/6J mice, including hypertension, renal glomerular endotheliosis, intrauterine growth restriction, and altered placental morphology. Thus, we generally hypothesize that elevated AVP secretion is mechanistically involved in the pathogenesis of PE. Here, we tested the hypothesis that chronic infusion of AVP during gestation in mice would cause changes in the placental transcriptome which parallel changes documented in human PE. Placentas were collected on gestational day 12.5 from mice that received chronic saline or AVP (24 ng/hr) infusion through pregnancy and RNA‐sequencing was performed. Differential expression analyses revealed 87 transcripts, corresponding to 82 unique genes as well as 3 non‐coding RNAs, that were differentially expressed between AVP‐ and saline‐treated placentas (FDR < 0.1). Among the differentially expressed genes identified, six genes (Trpm2, Itih4, Ncmap, Sema3f, Scnn1g, Nfat5) had been previously associated with human PE. Ingenuity Pathway Analysis (IPA) identified that the disease and functional annotations significantly altered in AVP‐treated placentas included hypertension, preeclampsia, as well as cell death. As expected, IPA also identified likely canonical upstream mediators including AVP, desmopressin, and calcium signaling. Notably, Gene Set Enrichment Analysis (GSEA) and IPA did not uncover any enrichment for hypoxia‐associated signaling, suggesting that despite the PE‐like morphological and genetic signatures induced by AVP, AVP does not induce these phenotypes via placental hypoxia. Parallel in silico re‐analyses of a large published dataset from NCBI‐GEO (GSE75010) describing the transcriptomes of control and PE human placentas with various clinical covariates demonstrated that some subtypes of human PE similarly do not exhibit placental hypoxia. Collectively, these data highlight molecular phenotypes of PE induced within the placenta of mice by AVP, and highlight the potential utility of the AVP infusion approach to model specific subtypes of human PE.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Respiratory load compensation and perception during 10‐breath sustained inspiratory resistive loading in normal subjects
Authors: Davenport Matthew Paul , Feinstein Justin , Khalsa Sahib , von Leupoldt Andreas , Davenport Paul Wesley 
Published: June 2021

Increased load on the respiratory system is a key feature in various respiratory diseases, accompanied by ventilatory compensatory behavior and breathlessness. This increased inspiratory load is often prolonged, ranging from minutes to days, and requires the individual to adjust their breathing pattern to sustain alveolar ventilation and minimize the work of breathing, i.e. load compensation. Experimentally, this is often studied by breathing through resistive (R) loads. Most prior load compensation studies have used single breath loads within a range of adaptability for most individuals (0–40 cmH2O/l/s) to determine the load compensation mechanisms. However, during exacerbations of lung diseases, the individual must load compensate for multiple breaths against increasing load magnitudes that may exceed their ability to sustain alveolar ventilation. The aim of this study was to investigate load compensation in normal subjects when breathing for multiple breaths (10) through loads of increasing magnitudes greater than their expected ability to sustain alveolar ventilation. A threshold for load decompensation was hypothesized. Healthy participants were tested while breathing through a circuit with inspiratory flow‐resistive loads (R's: 0–100 cmH20/L/s). The loads were presented in random block order, each for 10 consecutive breaths and separated by unloaded breathing periods. The loads were presented in 2 trials, 2 times each per trial. Subjects estimated their perceived load intensity in one trial and unpleasantness in the other trial. A load compensation index (LCI) was calculated using breath phase duration and airflow. For R=0–25 cmH2O/L/s, respiratory load pattern was a load magnitude dependent increased maximum inspiratory pressure, decreased airflow, increased inspiratory duration and decreased expiratory duration. This resulted in a relatively constant total breath time, inspiratory volume, minute ventilation, PCO2, PO2 and LCI. However, decompensation was observed for R50 and R100 leading to declining minute ventilation and LCI. The results suggest, however, that increasing the duration of the R=50–100 load presentations would likely lead to hypoventilation and respiratory failure. The perception of inspiratory R load intensity and unpleasantness increased with load magnitude. The results suggest that high magnitude loads and/or long durations of loaded breathing result in increased affective response and decompensating respiratory pattern indicating that the individual is no longer able to sustain ventilation under these conditions.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 Agrimonia Pilosa Ledeb. on glucose tolerance and hepatic steatosis in ovariectomized rats fed high fat diet
Authors: Lee Young Min , Jang Hwan Hee , Park Mi‐Young , Bae Ji Hyun , Kim Jung Bong , Choi Jeong Sook , Kim Haeng Ran 
Published: June 2021

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. Development of an efficient therapeutic agent without side effects is needed to prevent or improve postmenopausal symptoms and diseases induced by estrogen deficiency. This study was performed to investigate the effects of water extract from Agrimonia pilosa Ledeb. on glucose and lipid metabolism in ovariectomized rats fed high fat diet. Female Sprague Dawley rats were sham operated or ovariectomized and after 3 weeks, assigned to the following groups: sham‐operated + high fat diet(S); ovariectomized + high fat diet (OVX); ovariectomized + high fat diet with 0.1% A. pilosa water extract (OVX+0.1A); ovariectomized + high fat diet with 0.5% A. pilosa water extract (OVX+0.5A). In our results, ovariectomy significantly increased body weight and dietary intake compare with sham group (p<0.05), however there was no significant difference in weight gain and dietary intake by A. pilosa treatment. Blood triglyceride, total‐cholesterol, and LDL‐cholesterol showed a tendency to decrease in A. pilosa supplemented groups. In glucose metabolism, we observed the blood glucose levels of the OVX+0.1A and OVX+0.5A groups were lower than those of the OVX group (p<0.05). Blood adiponectin concentration was also increased significantly by A. pilosa treatment in ovariectomized group (p<0.05). Additionally, we investigated the suppressive effect of A. pilosa aqueous extract on hepatic lipid accumulation. These effects were accompanied by reduced hepatic tissue expression of steatosis‐related genes. These data suggest that A. pilosa improves glucose tolerance and hepatic steatosis in ovariectomized rats.Support or Funding InformationThis study was supported by a research project of the National Institute of Agricultural Science of the Rural Development Administration, Republic of Korea (project no. PJ008554), and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2017R1C1B5018328).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective effect of Thymol essential oil from Thynus quinquecostatus extracts on UV irradiation‐induced skin aging by supressiong MMP‐1 expression and collagen degradation
Authors: Lee Tae Hoon , Jung Hana , Lee Sang Min , Park Yujin 
Published: June 2021

Solar ultraviolet (UV) radiation is a main extrinsic factor for skin aging, which causes impairment of skin integrity through the induction of matrix metalloproteinases (MMPs), such as MMP‐1. Thynus quinquecostatus extracts are considered as potent anti‐photoaging agents due to including various active ingredients. To identify anti‐photoaging agents, in the present study, we examined preventing effect of thymol essential oil from Thynus quinquecostatus extracts on UV‐induced skin photo‐damage. First, we determined that the treatment concentration of without cytotoxicity on thymol by MTT assay in HaCaT cells. Next, we examined the attenuation of antiaging activity that the determined of MMP‐1 gene and protein expression levels in UVB‐induced keratinocyte. As a result, it was confirmed that the thymol and Thynus quinquecostatus extracts dramatically decreased UVB‐induced expression of MMP‐1 in a dose‐dependent manner. Our data showed that thymol and Thynus quinquecostatus extracts significantly attenuated UV‐induced phosphorylation of mitogen‐activated protein kinase (MAPK) signaling components ERK1/2, JNK1/2, and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of thymol and Thynus quinquecostatus extracts on UV‐induced MMP‐1 production in human keratinocytes. Taken together, our findings suggest that tymole essential oil from Thynus quinquecostatus extracts is a protective agent for skin anti‐photoaging through the prevention of UV‐induced MMP‐1 production.Support or Funding InformationFunding from the Region Industry Total Information Service Program (R0004665), Republic of Korea, supported this work.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Physiological and Biomechanical Study about the Passive Diastolic Modelling of the Heart Failure Rabbits Causing by Aortic Arch Banding
Authors: Sun Xiaotong , Zhao Dongliang , Huo Yunlong , Tan Wenchang 
Published: June 2021

ObjectiveCardiovascular disease (CVD) is a major health problem world‐wide and can lead to congestive heart failure (HF). Aortic arch banding is a classic experimental scheme to establish the congestive HF model, when hypertension and cardiac hypertrophy occur to the rabbits. Left ventricular myofiber stress and strain analyzing is an effective biomechanical method to study congestive HF. Our target is to study the physiological and biomechanical behave of the congestive heart failure model.MethodBy aortic arch banding, we establish the heart failure model. 6 New Zealand white rabbits have been banded 30% at aortic arch. The rabbits are scanned by Computed Tomography after 2‐weeks and 4‐weeks separately. We developed a three‐dimensional finite element model, which can describe the rabbit ventricular geometry and fiber architecture in detail. At same time, the paraffin sections have be surveyed in pathology.ResultThe volumes of the hearts can be calculated by 3‐D reconstructed model, which range from 2338.99 mm3 (SD 84.06) at 2‐weeks to 3339.07 mm3 (SD 701.91) at 4‐weeks. The strain and stress get lower from 2‐weeks to 4‐weeks. A huge change can be found in pathology sections.ConclusionsWe find the changing pattern of the strain and stress. The law of heart failure in physiology and biomechanics were discussed.Support or Funding InformationThis research is supported in part by the National Natural Science Foundation of China Grant 11372010(Y Huo); Shenzhen Science and Technology Innovation Institution (China) Grant JCYJ20160427170536358 (Y Huo).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.