bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac output and total vascular conductance responses to simulated carotid hypertension in young women: exercise and ovarian hormones
Authors: Kim Areum , Fisher James P , Deo Shekhar H , Vianna Lauro C , Fadel Paul J 
Published: June 2021

Previously we reported that compared to men, young women during the early follicular (EF) phase of the menstrual cycle exhibited an enhanced carotid baroreflex (CBR) control of blood pressure (BP) to hypertensive stimuli at rest due to a predominant contribution of cardiac output (CO). Whether such changes are altered during exercise or by fluctuations in endogenous ovarian hormone concentrations is unknown. Thus, 5s pulses of neck suction (NS; −80Torr) were applied at rest and during steady‐state cycling at 50% heart rate (HR) reserve to activate carotid baroreceptors in 10 young women at 3 different menstrual cycle phases (EF, late follicular (LF), and mid luteal (ML)). Beat‐to‐beat HR and BP were measured. Stroke volume was estimated with Modelflow, and CO and total vascular conductance (TVC; CO/meanBP) were calculated. At rest, the change in CO was the major contributor in mediating BP changes to NS during all menstrual cycle phases (CO vs. TVC; 99±15% vs. −3±16%, EF; 105±22% vs. −10±25%, LF; 108±19% vs. −14±22%, ML; P>0.05). This effect was lost during exercise in which a greater contribution of TVC was observed (CO vs. TVC; 14±34% vs. 83±131%, EF; 16±10% vs. 84±9%, LF; 34±14% vs. 66±13%, ML; P>0.05). Our findings suggest that in contrast to rest, exercising women exhibit a greater involvement of TVC in the CBR control of BP to hypertension; an effect that is independent of menstrual cycle phase.Supported by R01HL093167
AVP infusion increases the expression of urea transporters and ER stress pathway genes in medullae of female mice with urinary concentrating defect
Authors: Booth Allyson , Cai Qi , Romero-Aleshire Melissa Jill , Chandra Surabhi , Brooks Heddwen L 
Published: June 2021

Abnormal proliferation in collecting duct cells plays a crucial role in polycystic kidney disease (PKD) and in lithium‐induced renal dysfunction. Females with PKD demonstrate lower proliferation rates than males, resulting in a less severe phenotype. We previously reported that vasopressin induced an increase in renal cell proliferation in male AQP1KO mice in addition to ER stress gene activation. In this study we infused AVP for 14 days into female AQP1KO mice. AVP induced a small but significant increase in urine osmolality (155 mosmol/kgH20 vs control). 14 days AVP infusion significantly increased the expression of UTA1 and UTA3 mRNA 2.97 ± 0.29 and 3.34 ± 0.57, respectively, vs control. AQP2 and AQP3 mRNA also increased 3.52 ± 0.28 and 2.59 ± 0.23, vs control. AVP infusion significantly increased the mRNA expression of early growth response gene Egr‐1 2.49 ± 0.49 and transcription factors ATF3 and ATF4 mRNA; 4.91 ± 0.70, and 3.36 ± 0.25, vs control. AVP infusion significantly increased the expression of ER stress factor GADD153 mRNA 2.53 ± 0.41 vs control. AVP did not increase the mRNA expression of PCNA in female kidneys; PCNA is a marker of proliferation. These data suggest that vasopressin regulation of urea transporters is intact in female AQP1KO mice. Further studies will determine if vasopressin induced proliferative pathways are blunted in female AQP1KO mice.Support: DK073611 (HLB)
Alterations of Zinc, Copper, and Magnesium Concentrations During and After Open Heart Surgery
Authors: YAN Ying-Qun , LIU Xiao-Cheng , JING Wen-Bin , BAI Xiao-Yan , YANG Qin , HE Guo-Wei 
Published: June 2021

Trace elements such as copper (Cu), cobalt, and arsenic may contribute to myocardial dysfunction and Zinc (Zn) deficiency may increase the susceptibility of the phospholipid cell membrane to free‐radical damage and oxidative changes. Magnesium (Mg) is an important determinant of the resting membrane potential of cardiac cell membranes. We studied the concentration of these elements in cardiac surgery. Fifty‐four consecutive patients for elective coronary artery bypass grafting (CABG) (30) and valve replacements (VR) (24) were studied. Blood samples were collected every 30 min (T1–T5) during cardiopulmonary bypass (CPB) and postoperatively (T6–T9). Plasma Cu, Zn, and Mg were measured with flame atomic absorption spectrophotometry. The concentrations of Zn, Cu, and Mg were significantly different during and after CPB (p<0.01). The Zn concentration at T7 and T8 (p<0.01) and the Cu concentration at T1, T9 (p<0.05) were significantly different between two groups. However, the Mg concentration had no significant difference between two groups (p>0.05). In patients undergoing VR or CABG, the concentrations of Zn and Cu decreased considerably during CPB and recovered after CPB with more rapid recovery of Zn in CABG than VR patients whereas Cu concentration recovered more rapidly in VR patients. These may have significant clinical implications.Supported by International S&T Cooperation Program of China 2009DFB30560; National Basic Research Program of China 2010CB529502; Tianjin Municipal S&T Com 09ZCZDSF04200 & 10JCYBJC26400; NSFC 81170148; GRF CUHK4789/09M; CUHK2041688.
Effects of bioactive salmon peptides and fatty acids on cellular transport and secretion of adiponectin
Authors: DeClercq Vanessa , d'Eon Brandon , McLeod Roger 
Published: June 2021

Plasma adiponectin levels are inversely related to several components of the metabolic syndrome and therapeutics that target adiponectin secretion are emerging. Consumption of fish oil is associated with improved metabolic profile, however, there is additional evidence that the protein component of fish may also have metabolic benefits. The aim of this study was to examine the effects of fish fatty acids and peptides on adiponectin assembly and secretion in differentiated 3T3‐L1 adipocytes. Treatment with polyunsaturated fatty acids (PUFAs) increased total cellular adiponectin levels but did not increase adiponectin secretion. In addition, two fractions of molecular weight fractionated (<1000 dalton) salmon peptides, but not cod peptides, stimulated adiponectin synthesis and secretion. Subcellular fractionation on sucrose density gradients revealed that the majority of cellular adiponectin is located in the endoplasmic reticulum (ER). Treatment of the cells with Brefeldin A prevented adiponectin secretion and caused cellular accumulation of the high molecular weight adiponectin oligomers. These data suggest that the ER is an important site of cellular adiponectin accumulation and that treatment with PUFAs or salmon peptides can increase adiponectin in this adipocyte model.Grant Funding Source: Heart and Stroke Foundation of Canada and Natural Sciences and Engineering Research Council of Canada
Inhibition Of The Estrogen‐Mediated Cardiac Vagal Control Accounts For The Baroreflex Depressant Effect Of Chronic Nicotine In Female Rats
Authors: El-Mas Mahmoud M , El-Gowelli Hanan M , Fouda Mohamed A , El-gowilly Sahar M 
Published: June 2021

We previously showed that chronic nicotine dose‐dependently attenuated reflex chronotropic responses in female rats. Here the hypothesis was tested that impairment of the estrogen‐dependent cardiomotor vagal control mediates the nicotine‐baroreflex interaction. Baroreflex curves relating changes in heart rate to increases (phenylephrine, PE) or decreases (sodium nitroprusside, SNP) in blood pressure were constructed in sham‐operated, ovariectomized (OVX), and estrogen‐replaced OVX (OVXE2) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRSPE and BRSSNP). In sham rats, nicotine (2 mg/kg/day for 14 days) produced no changes in basal BP but reduced BRSPE and BRSSNP, suggesting attenuation of reflex bradycardic and tachycardic responses. Compared with sham rats, OVX selectively decreased BRSPE but not BRSSNP and abolished the nicotine‐induced impairment of both responses. The effects of OVX were reversed after treatment with estrogen or with the estrogen receptor modulator raloxifene. Atropine reduced BRS to comparable levels in all rat preparations regardless of the estrogen or nicotine milieu. Thus, nicotine attenuates reflex chronotropic activity via inhibition of the estrogen‐mediated facilitation of vagal cardiomotor activity.This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No. 502.
Enhanced maturation of induced pluripotent stem (iPS) cell‐derived neurons by astrocyte‐conditioned medium: roles of differential regulation of Ca2+ channel and GABAA receptor activities
Authors: Rushton David James , Mattis Virginia B , Svendsen Clive N , Arjomand Jamshid , Allen Nick D , Kemp Paul J 
Published: June 2021

Astrocytes promote synaptogenesis in vitro, a development which may be crucial to generating appropriate stem cell derived models of neurodegenerative diseases. However, the mechanism(s) by which they exert such effects are currently unknown.We investigated the influence of mouse striatal astrocyte conditioned medium, at 7, 14 and 21 days, on the differentiation and maturation of human iPS‐derived neuroprogenitors using whole‐cell patch‐clamp and Ca2+ imaging. Although the proportion of cells able to fire an action potential in response to depolarization was unaffected, the conditioned medium evoked: i) significant hyperpolarization of the membrane at rest; ii) upregulation of L‐, N‐ and R‐ type Ca2+ channel function, and; iii) a dramatic increase in the proportion of spontaneously active cells.Increasing the extracellular [Ca2+] from 0.6 to 1.8 mM resulted in accelerated neurogenesis and mimicked the enhanced maturity seen with astrocyte conditioned medium. These effects were blocked using specific inhibition of N‐ and L‐ type Ca2+ channels or GABAA receptors.Taken together, these data demonstrate a clear role for GABAA‐evoked depolarization, and consequent voltage‐gated Ca2+ influx, in the process of neuronal maturation, and suggest that astrocytes may promote synaptogenesis, at least in part, via increased gain of the GABA excitation pathway.Funded by MRC and CHDI.
Matrix Metalloproteinase‐1 Mediated Upregulation of VEGFR2 in Endothelial Cells
Authors: Alsaigh Tom , Mazor Rafi , Schmid-Schonbein Geert 
Published: June 2021

Matrix metalloproteinases (MMPs) have a critical role in vascular remodeling, tumor progression and angiogenesis. VEGFR2, the main receptor for VEGF, expressed on endothelial cells has a role in promoting cell survival, proliferation and angiogenesis. Since MMP‐1 expression is positively correlated with a variety of cancers, we tested the hypothesis that MMP‐1 has a direct effect on endothelial cells, specifically by increasing their levels of VEGFR2. Endothelial cells were treated with active MMP‐1 and analyzed for VEGFR2 mRNA, protein levels and specific signaling pathways governed by the receptor. We found that treatment with MMP‐1 significantly augmented mRNA levels and protein expression of VEGFR2 in endothelial cells. Furthermore, VEGF‐A dependent phosphorylation of intracellular signaling molecules such as ERK and Akt were higher in MMP‐1 treated cells. We conclude that MMP‐1 promotes VEGFR2 expression on endothelial cells and provides, at least in part, a mechanism by which MMPs in a tumor microenvironment can promote cell proliferation and angiogenesis.Research supported by NIH grant HL 10881
The effect of β2 adrenergic‐receptor stimulation on lung fluid balance in heart failure
Authors: Taylor Bryan Joseph , Ceridon Maile , Snyder Eric , Olson Thomas , Johnson Bruce David 
Published: June 2021

BackgroundIncreased pulmonary capillary pressure and a possible desensitization of lung β2 adrenergic receptors (β2AR) involved in fluid removal mechanisms may increase extravascular lung water (ELW) in stable heart failure (HF) patients. Whether these patients exhibit increased ELW remains controversial.PurposeTo determine if HF patients have elevated ELW versus controls (CTL) and if acute β2AR agonist inhalation stimulates fluid removal.Methods/Results14 stable HF patients and 19 healthy age/gender matched CTL were studied. Lung tissue volume (Vtis) (includes tissue, blood and water) and pulmonary capillary blood volume (Vc) were assessed pre and post nebulized albuterol via CT and rebreathe, respectively. ELW was derived as Vtis – Vc. Pre albuterol, ELW was greater in HF vs. CTL (861±241 vs. 739±143 ml, P<0.01), with no difference in Vtis (938±246 vs. 830±151 ml, P=0.08). Albuterol decreased Vtis (–4±2%, P=0.02) but did not change ELW (739±143 vs. 724±132 ml) (P>0.05) in CTL. In HF, albuterol decreased both Vtis (–5±3%) and ELW (– 4±2%) (P<0.05). There was a negative relationship between baseline values and the pre to post albuterol change for Vtis (r2=0.38) and ELW (r2=0.42) (P<0.01) in HF.ConclusionLung fluid is elevated in stable HF patients relative to healthy subjects. Stimulation of β2ARs appears to enhance fluid removal in HF, especially in patients with elevated lung water at rest.
Hemodynamic response after hypovolemic shock and resuscitation with low‐volume 6% hetastarch (HS) and high‐volume lactated Ringer's (LR) solution
Authors: Nunez Fiesky A. , Kislukin V. , Smith T. L. , Callahan M. F. , Burnett L. , VanDyke M. E. 
Published: June 2021

Treatment of hypovolemia is a severe medical problem. HS is thought to be best, each ml restores 1.6ml of circulating volume (CV) while 1 ml of LR restores 0.25ml of CV. Researchers use HS in a volume equal to shed blood and 3:1 resuscitation with LR. HS is not used clinically in that manner and it remains unknown how HS low‐volume resuscitation compares with large volume LR.Male SD rats were anesthetized with isoflurane, instrumented with an arterial catheter for mean arterial pressure (MAP) monitoring and carotid to jugular loop with flowprobes for ultrasound dilution cardiac output readings. Rats were hemorrhaged to a MAP of 40mmHg, maintained for 30 minutes then randomized to receive: 1) HS 6% @ 20% estimated total blood volume or 2) LR @ 3X the volume of shed blood. Hemodynamic parameters were taken at baseline, prior to resuscitation and 2 hours later. HS recovered cardiac function and central blood volume better than LR. However, HS volume expansion was so intense that Hct was so diluted it resulted in a calculated oxygen delivery equal to LR. HS caused a steep increase in HR after 60 minutes, with increased heart work. Such increase in heart work is detrimental to a strained myocardium and could result in early fatigue/failure. HS causes exaggerated osmosis that dilutes Hb and clotting factors, which may exacerbate ischemia and trigger dilutional coagulopathy. US Army uses HS for combat theater resuscitation. Civilian trauma centers still use high‐volume crystalloid resuscitation. This study helps clarify the physiology of low‐volume resuscitation.
The Role of Green Tea and Oxidative Stress in Heart Remodeling Induced by Tobacco Smoke Exposure
Authors: Pereira Elenize Jamas , Minicucci Marcos , Polegato Bertha , Portugal Priscila , Batista Diego , Modesto Pamela , Fernandes Ana Angelica , Rafacho Bruna , Matsubara Luiz , Zornoff Leonardo , Paiva Sergio , Roscani Meliza , Azevedo Paula 
Published: June 2021

The objective of this study is to evaluate the role of green tea (GT) in heart remodeling induced by exposure to tobacco smoke (ETS).MethodsWistar rats were allocated in 3 groups: C (control – standard diet); S (smoke – standard diet); SGT (smoke + diet with GT 0,25%). After 2 months, animals were submitted to echocardiography, isolated heart study, and oxidative stress evaluation. One way anova test was performed.ResultsETS leaded to an increase in left atrium area (C 0, 21±0, 03 ; S 0, 24±0,032; SGT 0, 2±0, 031) (p=0,02). End diastolic ventricle diameter/weight (p=0,5) and ventricle mass index (p=0,8) were similar. ETS impaired Systolic function: shortness fraction (C 59,5± 2,8; S 53,9±5, 9; SGT 54,5±4, 1) (p=0,03). No fibroses was evidenced: Hydroxyproline (C 2, 7±0, 6; S 3,0 ±0, 2 ; SGT 2, 9±0, 5 ) ( p=0, 5 ) ETS increased oxidative stress, that was attenuated by GT: hydroperoxides (C 133,4±14,6; S 175,9±11,5; SGT 132,0±15,4) (p<0,001); catalase [C 80,5(78,3–86,1); S 65,6(46,7–76,8); SGT 112,4(82,5–129,4)]; superoxide dismutase (C 19,5±1,9; S 11,2±0,8; SGT 19,9±2,2)(p<0,001); glutathione peroxidase (C 37,4±4,8 S 17,5±3,9 SGT37,8±3,7) (p<0,001).ConclusionIt is possible that GT attenuates cardiac remodeling induced by ETS in part due to reduction of oxidative stress.
Inhibition of phosphodiesterases relaxes urinary bladder smooth muscle via activation of the large conductance voltageand Ca2+‐activated K+ channels
Authors: Xin Wenkuan , Cheng Qiuping , Soder Rupal P. , Petkov Georgi V. 
Published: June 2021

Our previous studies showed that activation of cAMP signaling pathways reduces urinary bladder smooth muscle (UBSM) contractility by increasing the large conductance Ca2+‐activated K+ (BK) channel activity. Utilizing isometric UBSM tension recordings and the perforated patch‐clamp technique, we tested the hypothesis whether inhibition of phosphodiesterases (PDEs) can reduce guinea pig UBSM excitability and contractility by increasing BK channel activity. Inhibition of PDEs by 3‐isobutyl‐1‐methylxanthine (IBMX) concentration‐dependently reduced UBSM spontaneous and carbachol‐induced phasic contractions. IBMX also reduced electrical field stimulation (0.5–50 Hz)‐induced contractions of UBSM strips. Blocking BK channels with paxilline diminished the inhibitory effects of IBMX on UBSM contractility. IBMX increased the transient BK currents (TBKCs) frequency by ~3‐fold. However, IBMX did not affect the depolarization‐induced steady‐state whole‐cell BK currents. IBMX increased the frequency of the spontaneous transient hyperpolarizations by ~2‐fold and hyperpolarized the UBSM cell resting membrane potential by ~6 mV. Blocking the BK channels abolished the IBMX effect on the resting membrane potential. Our data reveal that PDEs inhibition with IBMX relaxes guinea pig UBSM via TBKCs activation and subsequent UBSM cell membrane hyperpolarization.Supported by NIH DK084284 to G.V.P.
The manner of metabolism is different between the atrium and the ventricle
Authors: Shimura Daisukie , Jiao Qibin , Kashikura Kasumi , Endo Keiko , Soga Tomoyoshi , Goda Nobuhito , Minamisawa Susumu 
Published: June 2021

Energy of the cardiac muscle largely depends on fatty acid oxidation (FAO). It is known that the atrium and the ventricle have tissue‐specific functions, structures, gene expressions, and pathologies. The ventricle pumps blood and its muscle wall is thicker than atrial wall. Thus, energy utilization should be different between them. However a tissue‐specific pattern of cardiac metabolism remains incompletely understood. Recently, innovative techniques have enabled comprehensive analysis of metabolites. Therefore, we aimed to clarify differences between the atrium and the ventricle and used male C57B6 mice at the age of 6 weeks to comprehensively measure metabolites of their atria and ventricles by capillary electrophoresis and mass spectrometry.We found that the metabolic pattern was significantly different between them. The levels of lactate, acetyl CoA, and succinate in the ventricles were higher than the atrium. Moreover, N‐acetyl aspartate (NAA) and acetylcholine were higher in the atrium than the ventricles.Our data suggest that energy metabolism of the ventricle is more active than the atrium and depends on not only FAO but also glycolysis with lactate fermentation, whereas that of the atrium largely depends on FAO. Furthermore, the atrium is innervated and NAA might be a molecular marker of it.We hope these findings contribute to better understanding of tissue‐specific characters and pathologies.
Hypoxia‐induced muscle atrophy involves direct and indirect signaling towards protein turnover regulation
Authors: De Theye Chiel Charles , Koehler S Eleonore , lamers Wouter H , Schols Annemie M.W.J. , Langen Ramon J.C. 
Published: June 2021

BackgroundAs COPD patients may experience hypoxemic episodes, we hypothesized that subsequent tissue hypoxia is a trigger of COPD‐associated skeletal muscle atrophy.MethodsMice were kept under normoxia or hypoxia. Oxygen levels were reduced stepwise to 8% during 48h, and maintained for 21 days. Food intake was monitored and mice were sacrificed at days 4 and 21. To discern direct and indirect effects of hypoxia, fully differentiated C2C12 myotube cultures were exposed to hypoxia (4% O2).ResultsHypoxia induced hypoxemia, acidosis, erythremia. Gastrocnemius muscle weight decreased, which was only in part attributable to hypophagia. Comparing hypoxia with pair‐fed, expression of ER‐stress markers Atf4 and Gadd34, were increased as a direct effects of hypoxia and at day 4 partially by hypophagia. Protein synthesis was induced evidenced by reduced p‐eIF2α levels and increased mTOR signaling. Foxo‐1 activity and expression were directly induced by hypoxia and at day 4 by hypophagia. Gene expression associated with autophagy and ubiquitin 26S proteasomal degradation was induced and at day 4 partially attributable to hypophagia. As opposed to MuRF1, Atrogin‐1 and LC3B, Bnip3 expression was directly regulated by hypoxia.Conclusion: Hypoxia‐induced muscle atrophy is characterized by signaling suggestive of increased muscle protein turnover.Supported by the Dutch Top Institute Pharma (project # T1‐201).
Multiple Players Vying for One Target: Regulation of Differential Signaling Fate of Corticotropin‐releasing Factor Receptor 1 (CRF1)
Authors: Mahajan Shilpi , Hasdemir Burcu , Liao Min , Bhargava Aditi 
Published: June 2021

Activation of CRF1 by CRF, urocortin (Ucn1) or both, is critical in stress‐related pathophysiological conditions like anxiety, depression, and irritable bowel syndrome. We sought to determine how CRF1 activation by multiple ligands evokes distinct cellular responses. Mass spectrometry and HPLC showed endothelin‐converting enzyme‐1 (ECE‐1) differentially degrades CRF and Ucn1; ECE‐1 cleaves Ucn1, but not CRF, at critical residue Arginine‐34/35’, which is essential for ligand‐receptor binding. ECE‐1 cleavage disrupts the Ucn1‐CRF1 complex to alter Ucn1‐, but not CRF‐mediated Ca2+ mobilization. ECE‐1 inhibition disrupted Ucn1‐, but not CRF‐induced CRF1 recycling and re‐sensitization, but did not prolong the association of CRF1 with β‐arrestins (βARRs). Ucn1‐, but not CRF‐induced CRF1 recycling was dependent on Rab11 activity and re‐sensitization was dependent on both Rab4 and Rab11 activity. CRF1 behaves like a class A GPCR with respect to transient βARR interaction, but like a class B GPCR with respect to slow recycling. We propose a novel mechanism by which two ligands acting on the same receptor can result in distinct re‐sensitization and downstream signaling– differential degradation by ECE‐1.NIH DK080787 and Hellman Family Foundation grant to AB.