bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet activating factor (PAF) induces s‐nitrosylation of signalling proteins in an endothelial cell line
Authors: González Francisco G , Sánchez Fabiola A , Velarde Victoria , Boric Mauricio P , Durán Walter N 
Published: June 2021

In endothelial cells PAF increases microvascular permeability to macromolecules through activation of endothelial nitric oxide synthase (eNOS). In these cells NO signalling determines reorganization of intercellular contacts and the consequent loss of endothelial barrier stability, whereas the action of small GTPases keeps this barrier stable. It is not known whether PAF increases the permeability by NO‐mediated protein S‐nitrosylation and/or increased guanylate cyclase (sGC) activity and whether this inflammatory ligand modifies the activity of small GTPases that could be regulated by guanine exchange protein directly activated by cAMP (Epac). We studied the effect of PAF: 1) on s‐nitrosylation of signalling proteins using the biotin switch and 2) on the activity of small GTPases Rac1 and Rap1, using fusion proteins and pull down techniques, in the cellular line ECV stably transfected with eNOS‐GFP cDNA (ECV‐eNOS‐GFP). PAF stimulation increased s‐nitrosylation of eNOS, Epac, sGC, Rap1 and Rac1, in a cyclic way, with maximum increases at 30 s and 15 min post stimulus. Rap1 and Rac1 activity did not change with PAF stimulation. These results suggest that PAF increases permeability to macromolecules by s‐nitrosylation of signalling proteins, which could represent a change in their activity, however, not involving small GTPases Rap1 and Rac1.Supported by Grants NIH‐5RO1‐HL070634 and FONDECYT 1090757.
The aortic and carotid sinus baroreflexes contribute equally to control blood pressure and heart rate variabilities
Authors: Tang Xiaorui , Hu Tian , Snyder John S 
Published: June 2021

Baroreflexes are important in stabilizing blood pressure (BP). Disrupting the reflexes, e.g., via sinoaortic denervation (SAD), largely increases BP variability (BPV), which contributes to end‐organ damage. Because baroreflexes are often destructed separately in clinic, this study examines the individual role of aortic and carotid baroreflexes in BPV.Seven neuromuscular blocked (NMB), Sprague‐Dawley, female (225–275 g) rats were studied. Aortic denervation (AD, 4 rats) and carotid denervation (CD, 3 rats) were made sequentially, with initial denervation chosen in random order. BP and heart rate (HR) were recorded continuously for 10 hrs during baseline and denervation stages. BPV was defined by standard deviation (SD), and very low frequency (0.01–0.2 Hz) power of the BPV spectrum. Results: 1) Independent of denervation order, complete SAD greatly increased BPV: Compared to the baseline, SDs and VLF powers increased ~250% (AD→SAD: t=7.15, p<.01; CD→SAD: t=12.75, p<.01) and 130% (AD→SAD: t=10.59, p<.01; CD→SAD: t=9.78, p=.01), respectively; 2) AD and CD each increased BPV: SDs increased ~100% and VLF powers ~80%; the increase was significant for AD (SD: t=8.88, p<.0; and VLF: t=4.16, p<.05), but not for CD. There was no difference between post‐ AD and CD BPV; and 3) Denervations had no effect on HR variability. Conclusion: Aortic and carotid baroreflexes contribute equally to BP and HR variabilities.
Store‐operated Ca2+ influx predicts coronary artery disease and is induced by dyslipidemia in metabolic syndrome and type 2 diabetes
Authors: Neeb Zachary P , Alloosh Mouhamad , Edwards Jason , Bratz Ian N. , Sturek Michael 
Published: June 2021

ObjectiveWe tested the hypothesis that dyslipidemia was the principal component of metabolic syndrome (MetS; “prediabetes”) in the progression to type 2 diabetes and increased store‐operated Ca2+ entry (SOCE) in coronary smooth muscle that contributes to coronary artery disease (CAD). Accordingly, we focused on and eliminated dyslipidemia from MetS allowing the contribution of dyslipidemia to be determined.Methods and resultsOssabaw swine, an excellent humanoid model of MetS, were fed normal chow (Lean; N=9), high fructose diet that induced normolipidemic MetS (NMetS; N=6), or high fructose/trans‐fat/cholesterol diet that induced dyslipidemic MetS (DMetS; N=7) for 24 weeks before being assessed for MetS and CAD. NMetS did not develop MetS, type 2 diabetes, increased SOCE, or CAD. DMetS developed MetS with type 2 diabetes, increased SOCE, and CAD. Swine fed the same atherogenic diet as DMetS, but short‐term (sDMetS; N=3), developed dyslipidemic MetS with increased SOCE preceding CAD. Electrophysiology of coronary smooth muscle revealed absent Ca2+‐induced cation conductance and increased monovalent cation (Na+) permeance via store‐operated channels in DMetS compared to Lean.ConclusionsTaken together, our results demonstrate dyslipidemia is the primary contributor to increased SOCE and the development of type 2 diabetes that precedes CAD in the metabolic syndrome.
Lung arginase activity is increased in ovine model of acute lung injury and contributes to long term pulmonary dysfunction
Authors: Sousse Linda , Yamamoto Yusuke , Enkhbaatar Perenlei , Yu Young‐Ming , Rehberg Sebastian , Traber Lillian , Herndon David , Traber Daniel 
Published: June 2021

Thermally injured children who have sustained inhalation injury show evidence of restrictive lung disease during their recovery period. We hypothesize that lung arginase activity is increased by burn and inhalation injury, leading to increased collagen deposition in the lung and contributing to long‐term pulmonary dysfunction.METHODSEwes were randomly divided into (1) Uninjured: n=6 and (2) injured: n=7 groups. The injured animals were subjected to 20% TBSA burn and 36 breaths of cotton smoke under deep anesthesia.RESULTSDDAH‐II, an enzyme that degrades ADMA, which is an endogenous inhibitor of NOS, significantly decreases after 2 and 3 weeks in the lung compared with uninjured animals. Lung ADMA increases from 2 to 3 weeks. Expression of iNOS significantly decreases in the lung 2 weeks after injury compared with uninjured animals. Lung arginase activity and hydroxyproline, a marker of collagen deposition, increase with 3 weeks post‐injury compared to the uninjured animals. The increases in arginase and collagen are associated with reduced gas exchange and lung diffusion capacity after 3 weeks compared to uninjured animals.CONCLUSIONThe decrease in DDAH‐II results in increased ADMA, resulting in decreased NOS. The decrease NOS causes an increase in arginase activity because NOS forms NOHA, which forms NO and inhibits arginase. The increase in arginase activity contributes to the increase in collagen deposition, which leads to long‐term pulmonary dysfunction. Interruption of this pathological chain reaction may be useful in preventing the long‐term sequelae of the smoke inhalation and burn injury.
Interstitial adenosine but not nitric oxide concentrations are elevated during systemic hypoxia in rat skeletal muscle
Authors: Smith Ashley A. , Zhao Yi , Fabris Sergio , MacLean David A. 
Published: June 2021

During systemic hypoxia it is generally accepted that nitric oxide (NO) and adenosine (Ado) contribute to peripheral vasodilatation in skeletal muscle. To examine this, microdialysis fibers were inserted into the gastrocnemius muscle of anesthetized rats (n = 16) and perfused with ringers (control), 60 μM ATP (Ado precursor) or 500 μM AOPCP (5′ectonucleotidase inhibitor) at a rate of 5 μL/min during rest and hypoxia (10.5% O2). During all perfusions and conditions no changes in interstitial NO concentrations were observed. Interstitial Ado levels during ringers perfusion were 0.04±0.01 μM at rest and increased to 0.07±0.01 μM during hypoxia (P<0.05). The perfusion of ATP alone increased (P<0.05) interstitial Ado levels from 0.04±0.01 μM to 0.12±0.02 μM at rest and hypoxia further increased (P<0.05) Ado levels to 0.18±0.02 μM. Perfusion of AOPCP reduced interstitial Ado to undetectable levels throughout the experiment, confirming inhibition of the 5′ectonucleotidase and subsequently Ado production. These data clearly demonstrate that hypoxia and alterations in Ado concentrations do not directly affect NO concentrations. In particular, when Ado production was inhibited, NO did not compensate for the loss of this vasodilator, even during hypoxia. Furthermore, interstitial Ado levels were elevated during hypoxia and appear to play a key role in interstitially mediated vasodilation.Supported by NSERC.
Endothelin‐1 induces smooth muscle cell plasticity in small mesenteric arteries
Authors: Schoorl Marieke , Bakker Erik N , de Vos Judith , vanBavel Ed 
Published: June 2021

AimSmall arteries show eutrophic inward remodeling in response to many physiological and pathological stimuli. We hypothesized that early events include repositioning and adapted architecture of smooth muscle cells, reflected by shifts in active length‐tension relations.MethodsRat mesenteric arteries were incubated overnight in a wire myograph at low (0.4 D100) or high (1.1 D100) distension with or without 10 nM endothelin‐1 (ET‐1). D100 is the passive diameter at an equivalent pressure of 100 mmHg. Before and after incubation, active (125 mM K+) and passive force‐length relationships were determined by stepwise distension of the vessel.ResultsSegments (n=10) incubated with ET‐1 at 0.4 D100 showed a marked leftward shift of the force‐length curve. Optimal force developed at 0.90±0.02 D100 (day 0) versus 0.84±0.02 D100 (day 1, p=0.03). This shift did not occur in the absence of ET‐1. At 1.1 D100 incubation, slight rightward shifts occurred.Conclusionmaintained activation at low diameter shifts tension‐generating properties, possibly forming an early event in inward remodeling. This study was performed within the framework of the Dutch Top Institute Pharma project T2‐108.
Intracellular calcium stores contribute to the myogenic response of rat cerebral arteries
Authors: Tam Raymond , Kerr Paul M , Plane Frances 
Published: June 2021

Cerebral blood flow is controlled by autoregulatory mechanisms which maintain blood flow within narrow limits despite large changes in blood pressure. Increases in blood pressure cause small cerebral arteries to constrict, a mechanism called the myogenic response. We investigated the contribution of intracellular calcium stores to the development of myogenic tone in rat middle cerebral arteries.Cerebral arteries mounted in a pressure myograph were subjected to stepwise increases in intra‐vascular pressure (20–120 mmHg), and changes in vessel diameter were recorded in the presence or absence of drugs. Cyclopiazonic (CPA; 10 μM), an inhibitor of the SR Ca2+‐ATPase, attenuated myogenic tone at 80mmHg by 64.2 ± 7.2% (n=5). Caffeine (10 mM), a ryanodine channel opener, reduced myogenic tone by 80.3 ± 6.7% (n=5). The effect of caffeine was not inhibited by iberiotoxin (IBTX 100nM; n=4), a large conductance calcium‐activated potassium channel (BKCa) blocker, suggesting that activation of BKCa is unlikely. When CPA was added in combination with nifedipine (10 μM), an L‐type calcium channel blocker, development of myogenic tone was abolished. In conclusion, our data suggests that release of intracellular calcium from the SR plays an important role in the development of myogenic tone in rat middle cerebral arteries. Funded by Heart and Stroke Foundation and University of Alberta Queen Elizabeth II Award.
Regulation of voltage‐gated calcium channel expression by estrogen
Authors: Dalton Jamie , Joseph Biny K. , Rusch Nancy J. , Hill Brent J.F. 
Published: June 2021

We previously demonstrated that a physiological estrogen (E2) concentration decreases the protein expression of the voltage‐gated calcium channel (VGCC) pore‐forming α1C subunit in coronary arteries. However, it is not known how E2 elicits this effect. In this study we hypothesized that the E2 mediated down‐regulation occurs via a posttranscriptional pathway in arterial smooth muscle. Right coronary arteries were obtained from hearts of mature sows. The distal end of the artery was cut into longitudinal strips, and the endothelium was left intact or mechanically removed. The strips were incubated for 24 hours in E2 (1 nM) or its ethanol solvent. Using RT‐PCR our data suggest that E2 has no effect on the mRNA expression of the VGCC α1C subunit. Preliminary results from Western blots indicate that the decrease in VGCC expression by E2 is endothelium‐independent. Our findings provide important insights into the mechanistic pathway of the E2 mediated down‐regulation of VGCCs. Because vascular disease is accompanied by endothelial damage, the presence of circulating E2 may have beneficial effects to limit coronary vasoconstriction.Support: NCRR of the NIH, Grant #P20 RR‐16460
The Effect Of Ethanol On Tracheal Smooth Muscle Of Cat
Authors: Jakupaj Muharrem , Sopi Ramadan B , Lajçi Azem , Neziri Burim , Devaja‐Kumnova Shqipe , Krasniqi Avdyl 
Published: June 2021

Previously we have shown that ethanol induces contraction of pulmonary artery smooth muscle (PASM). However, the effect of ethanol on tracheal smooth muscle (TSM) and the mechanisms involved are not well understood. Therefore, we hypothesized that ethanol induces contractile responses of TSM and extra cellular Ca2+ is involved to this effect. In vitro force measurements were performed in TSM strips, excised from cats (n=29). Tissues were stabilized in Krebs‐Henseleit (KH) solution and treated with different concentrations of ethanol (46 – 276 mM). The role of extra cellular Ca2+ was studied by incubation of tissue in a Ca2+ free KH solution or using a Ca2+ channel blocker‐nifedipine. The role of nitric oxide (NO) was assessed by inhibition of NO synthase (NOS) using Nω‐nitro‐L‐arginine methyl ester. The ethanol induced concentration‐dependent contraction of TSM. Lack of Ca2+ in medium resulted with decrease of TSM tone likewise Ca2+ channel blocker. Inhibition of NOS, significantly increased contractile responses of TSM to the ethanol at lower ad middle concentrations, but reduced these responses at higher concentrations. In addition, inhibition of NOS significantly potentiated TSM tone to ACh.These data demonstrate that ethanol induces TSM contraction of cat and extra cellular Ca2+ is an important involved factor. NO release as a relaxant molecule counteracts the effect of ethanol and other agonists.
Increased PDK4 expression via PGC‐1α/ERRα – dependent mechanism in mouse skeletal muscle after high fat feeding
Authors: Rinnankoski‐Tuikka Rita , Torvinen Sira , Silvennoinen Mika , Lehti Maarit , Kivelä Riikka , Kainulainen Heikki 
Published: June 2021

The key regulator of cellular energy metabolism is the peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α). It is shown that PGC‐1α coactivates the pyruvate dehydrogenase kinase (PDK4) gene expression via the estrogen related receptor (ERRα). Our aim was to investigate the effects of high fat (HF) feeding and physical activity in the expression levels of these genes in the skeletal muscles of C57BL/6J mice.The HF animals showed an altered blood lipid profile suggesting changes in the overall lipid metabolism. The expression level of PGC‐1α was slightly down‐regulated after HF feeding, although voluntary wheel running restored the levels. Upregulation of ERRα and PDK4 was seen after HF diet and this combined with running had even more profound effects on the expression levels.Although HF diet did not increase the PGC‐1α mRNA levels, we hypothesize that the regulation of energy metabolism after HF feeding leads to a situation where PDK4 inhibits the glucose oxidation coincident with the increased mitochondrial fatty acid oxidation. Whether the fatty acid oxidation is reduced de facto after HF feeding, as the hypothesis on accumulation of ectopic lipids might suggest, remains to be further clarified. The research was funded by the Finnish Ministry of Education.
Training induced improvements in aerobic capacity can occur independent of PGC‐1[alpha] in aging human skeletal muscle
Authors: Konopka Adam , Reidy Paul , Jemiolo Bozena , Kaminsky Leonard , Trappe Todd , Trappe Scott , Harber Matthew 
Published: June 2021

The purpose of this investigation was to elucidate the molecular adaptations in skeletal muscle that occur with aerobic exercise training in elderly individuals. Muscle biopsies were obtained from the vastus lateralis of nine old women (70±2y) to determine basal mRNA and/or protein content of factors involved in mitochondrial biogenesis (TFAM, PGC‐1α, COX IV) before and after 12‐weeks of aerobic training on a cycle ergometer. Post training biopsies occurred ~48 hours after the last exercise session in order to assess steady state levels of select mRNA and/or protein. Whole body aerobic capacity increased (P<0.05) 30±9% and COX IV protein, a marker of mitochondrial content, was elevated (P<0.05) 33±7% after training. Interestingly, aerobic training did not alter the basal gene expression of PGC‐1α and TFAM. However, PGC‐1α protein content was reduced (P<0.05) 20±5% after aerobic training. These data suggest that increased basal levels of PGC‐1α are not necessary for the improvements in whole body and skeletal muscle oxidative capacity with exercise training in elderly women.Supported by grants NIH (AG032127) and NASA (NJ06HF59G)
Discrepancy between increased mTORC1 signaling and total muscle protein accretion after leucine stimulation
Authors: Haegens Astrid , Schols Annemie M , van Essen Anon LM , van Loon Luc JC , Langen Ramon C 
Published: June 2021

An important goal of nutritional intervention in muscle wasting disorders is to stimulate protein synthesis. The branched chain amino acids (BCAA), and leucine in particular have been suggested to promote protein synthesis via activation of the mammalian target of rapamycin (mTOR) pathway. The endpoints determined so far were mostly cell signaling parameters leaving the question open whether the activation of mTORC1 by leucine leads to protein accretion? The aim of this study was to investigate, in C2C12 cells cultured in the presence of physiological AA levels, whether the stimulating effects of leucine on mTORC1 lead to total and muscle specific protein accretion. Myoblasts were differentiated in DMEM diluted with HBSS (supplemented with NaHCO3) to yield culture medium containing glucose (1g/L), FBS (1%) and physiological AA levels (10% of unmodified DMEM) in presence or absence of 5mM leucine.Leucine stimulated the mTORC1 targets 4E‐BP1 and S6K1, measured by western blot. Creatine kinase activity and total protein accretion were not increased in cells that had differentiated in the presence of leucine for 5 days. Myosin Heavy Chain fast and slow, measured by western blot, were however increased under these conditions. These findings suggest a differential response of muscle proteins in the presence of leucine.
Effect of Acclimation to Intermittent Hypobaric Hypoxia on NO Homeostasis
Authors: Chang Jae Seung , Sim Yun Bok , Lee Jeong Hee , Nam Sang Seok , Sunoo Sub , Kong In Deok 
Published: June 2021

Hypoxia is one of the major stimuli to produce nitric oxide (NO). Recent studies have shown that conversion of nitrogen dioxide (NO2) to NO is independent of nitric oxide synthase (NOS) activity, and exercise is responsible for NO production by its reduction of metabolic products NOx, nitrite (NO2−)/nitrate (NO3−). This study was to examine the effects of training on NO homeostasis after high altitude exposure.Aerobic capacity (i.e., VO2max) and NO related molecules, cyclic guanosine monophosphate (cGMP), NOx or NO2, were measured by use of an fluorometric and enzyme immunoassay (EIA) analysis (Cayman Inc., USA) from bloods: Fourteen healthy exercisers comparatively corresponding to mountaineers during high‐intensity aerobic exercise who has climbed up 5,000 meters above the sea level, and volunteers who had 7 days before and after aerobic training on treadmill and bicycle ergometer based on 75% HR max and sleeping in hypobaric hypoxic conditions (3000m~5000m) for 4 days.VO2/75%HRmax of acclimation at an altitude of 5,000 meters was significantly increased by 21.45% (p = 0.0016). In addition, cGMP concentration in post‐training group (3.35 ± 1.082 pmol/ml) was also increased compared to pre‐training one (1.54 ± 0.751 pmol/ml) (p < 0.001), whereas NOx or NO2 concentration was decreased significantly (i.e., NOx, 16.49 ± 6.357 vs. 11.32 ± 2.805 μM, p = 0.0027; NO2, 12.62 ± 8.321 vs. 7.39 ± 2.273 nM, p = 0.0395) These findings suggest that increase of cGMP via an NO production may ameliorate physical activity at high altitudes, which is associated with the changes of systemic concentration of NOx and NO2.
High Skin Temperature Accentuates Aerobic Performance Degradation when Hypohydrated.
Authors: Kenefick Robert W. , Cheuvront Samuel N. , Ely Brett R. , Palombo Laura J. , Sawka Michael N. 
Published: June 2021

High skin temperature (Tsk) and hypohydration (HYPO) degrade aerobic performance, but the impact of Tsk on HYPO mediated performance degradation is unknown.Hypothesisgraded elevations in Tsk would proportionally reduce performance when HYPO. Thirty‐two males (22 ± 4 yrs; VO2peak, 45 ± 8 ml·kg−1·min−1) were divided into 4 matched cohorts (n=8) and then were tested during compensable heat stress in one ambient temperature (Ta; 10, 20, 30, 40°C) when euhydrated (EU) and HYPO (−4% body mass). Volunteers completed a 30‐min exercise bout (cycle ergometer, 50% VO2peak) and 15 min self‐paced time trial. Within EU and HYPO, core temperatures were similar across Ta, but Tsk was elevated proportionally, ~4°C Tsk per 10°C Ta. Total work (TW) expressed as % change from EU (with 95% CI), was degraded incrementally with increased Ta by −2.9% (−5.8 to 0.07) at 10°C, −5.1% (−10.62 to 0.40) at 20°C, −12.1% (−18.79 to −5.5) at 30°C and −22.9% (−40.5 to −5.4) at 40°C. The % decrement in TW from EU (y) was predicted (r=0.60, P<0.05) from Tsk (x), y=−1.650x+39.86 where each 1° elevation in Tsk yields −1.65% decline in TW. The HYPO mediated degradation in aerobic exercise performance is amplified with increasing skin temperature.Opinions contained herein should not to be construed as official views of the Army or DoD.
Low salt intake during pregnancy and lactation causes changes in energy metabolism in adult female Wistar offspring
Authors: Jang Karen Lucasechi Lopes , Furukawa Luzia Naoko Shinohara , Dolnikoff Miriam Stermann , Heimann Joel Claudio 
Published: June 2021

ObjectiveTo study some factors related with the energy metabolism in adult offspring of dams fed low salt diet during pregnancy and lactation.MethodsFemale Wistar rats were fed low (LS 0.15%) or normal (NS 1.3% NaCl) salt diet since 8 weeks of age. At 12 weeks of age, they were mated. Offspring were fed NS from weaning and at 12 weeks of age, they were kept on 4oC or room temperature (RT) during 24 hours. Body weight (BW) and temperature (BT), blood glucose (GLU) plasma norepinephrine (NOR), and leptin (LEP) were measured. Gene expression (RT‐PCR) for uncoupling protein‐1 (UCP1), coenzyme Q1 (Q1) and Q2 (Q2) was evaluated in brown adipose tissue.Results(mean±SEM, n=5 to 8/group): No differences were observed in BW between adult offspring groups. UCP1, Q1 and Q2 were lower (p<0.05) in LS (UCP1 ‐ 1.5±0.1, Q1‐ 0.7±0.1, Q2 ‐ 1.0±0.1) than in NS (UCP1 ‐ 2.0±0.1, Q1 ‐ 1.1±0.1, Q2 ‐ 1.3±0.1) at RT but not at 4°C. At 4°C BT decreased (p<0.05) in NS but not in LS. NOR (pg/dL) was higher on 4°C (471±42) than on RT (206±28) in NS but not in LS. GLU did not change after exposure to 4°C in NS and LS. At 4°C, LEP decreased (p<0.05) in NS but not in LS.ConclusionsLow salt diet during pregnancy and lactation modifies expression of some genes involved in energy metabolism in adult female offspring. Supported by FAPESP.