bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of aerobic training on the deposition of collagen fibers and glomerular proteoglycans in hypertensive rats
Authors: Batista Álvaro Martins , Alves Tatiana Pereira , El Chaar Laiali Jurdy , Souza-Oliveira Thais Cristina , Rabechi Nara Baptistella , Piva Camila Jesus , Jordão Maria Tereza , Viegas Katia Aparecida , Michelini Lisete Compagno , Lacchini Silvia 
Published: June 2021

This study evaluated if aerobic training (AT) improves glomerular morphology in hypertensive (SHR) and normotensive (WKY) rats. We used SHR and WKY male rats 10weeks‐age submitted or not to AT (1hr, 5 times/week) for 1, 2, 4, 8 and 12 weeks or kept sedentary for 0 and 12 weeks (n=8/each). Mean arterial pressure (MAP) and heart rate (HR) were recorded, and kidneys harvested for Bowmanˈs capsule (BC) evaluation. Results were compared by ANOVA, using p=0.05 as significant. Both WKY and SHR improved physical performance after 6 and 12 weeks of AT(S0:1.02±0.3 vs 1.62±0.4, T6:1.32±0.2 vs 2.09±0.3, T12:1.92±0.4 vs 2.40±0.4km/h). SHR decreased MAP and HR (179±10 vs 163±6mmHg, 394±18 vs 363±3bpm; on S0 vs T12). BC thickness showed greater deposition of collagen fibers in SHR compared to WKY (3.72±1.35 vs 1.98±0.25?m; on sedentary), and reduction after AT in SHR (1.79±0.24μm). Proteoglycan analysis showed an increased deposition induced by hypertension (1.34±0.41 vs 0.90±0.09μm; sedentary SHR vs WKY), and AT decreased this in both(SHR:1.34±0.41 vs 0.75±0.09μm, WKY:0.90±0.09 vs 0.65±0.02μm; S0 vs T12). We also observed that the time of hypertension increases deposition of proteoglycans (1.34±0.41 vs 1.64±0.48μm; S0 vs S12). The data suggest that AT induces glomerular remodeling, reducing glomerular fibrosis and glomerulosclerosis in SHR, and may be associated with the observed fall in MAP.Grant Funding Source : FAPESP
Differential Effects on Regional Pulse Wave Velocity & Augmentation Index Following Maximal Exercise in Healthy Young Men
Authors: New Karl James , Morgan Ashley , Harris Trevor , Fall Lewis , Brugniaux Julien , Bailey Damian M 
Published: June 2021

Nine young normotensive healthy males (24.6± 3.7 years; 75.4± 10.2 kg) MAP = 91 ± 6 mmHg were studied for 1‐hour following an incremental ramp protocol to VO2peak (56.2± 10.5 ml/kg/min) on an electronically braked cycle ergometer. Blood pressure was assessed via an automated blood pressure monitor (Datex‐Ohmeda, Finland). Regional limb pulse wave velocity (PWV) was determined simultaneously in the left arm and leg by oscillometry (QVL P84, UK) whilst contemporaneously determining central aortic stiffness (AIx) via aplannation tonometry (Sphygmocor, Atcor Medical, Australia). The operator index, which is an estimate of quality of the SphygmoCor derived waveforms, was above the recommended level with an average index of >80%. Following mathematical confirmation of distribution normality using the Shapiro‐Wilks test data were analysed with a repeated measures ANOVA and post‐hoc Bonferroni‐corrected paired samples T‐tests.During exercise there was an intensity‐related increase in MAP, heart rate and pulse pressure (P<0.01). Exercise decreased both systolic blood pressure across the 60‐minute recovery period (P<0.01) and MAP in the initial recovery from exercise (P<0.05). Upper limb PWV was reduced following exercise (P<0.05) whilst lower limb PWV was unchanged. AIx was elevated at the termination of exercise (P<0.05) but did not decrease below resting levels in the recovery period.These results indicate that in active healthy individuals acute exercise induces a systemic hypotension and increased arterial compliance in the upper limb vascular bed but not the lower limb vascular bed. Furthermore, estimated aortic stiffness and central pressure appears to remain un‐modified in the recovery from exercise. Hence there are clear differential responses in central and peripheral large artery haemodynamic recovery from exercise.
Acute Oral Ingestion of Ascorbic Acid Improves Muscle Blood Flow and Oxygen Consumption During Exercise In Older Healthy Humans
Authors: Richards Jennifer C. , Crecelius Anne R. , Kirby Brett S. , Garcia Leora J. , Larson Dennis , Luckasen Gary J. , Dinenno Frank A. 
Published: June 2021

Intra‐arterial infusion of ascorbic acid (AA) reverses the age associated blood flow impairment during mild handgrip exercise by improving endothelium‐derived nitric oxide bioavailability. We tested the hypothesis that acute oral AA would improve forearm blood flow (FBF) and oxygen consumption (VO2) during graded rhythmic handgrip exercise among older men (n=8; 65 ± 3 years). Subjects performed two bouts (15 minutes each) of graded rhythmic handgrip exercise (5, 15, 25% of maximum voluntary contraction (MVC)). Following trial 1 (control), participants ingested 2 g of AA and rested comfortably for 2 hours and repeated the exercise bout (trial 2). At rest and during exercise, we measured FBF (Doppler ultrasound) and calculated VO2 using deep venous blood samples. Compared to control, there was no influence of AA at rest or during 5% MVC exercise. AA significantly increased FBF (199 ± 13 vs. 248 ± 16 ml/min and 343 ± 24 vs. 403 ± 33 ml/min (P< 0.05)) and VO2 (262 ± 20 vs. 337 ± 28 ml/min and 433 ± 42 vs. 504 ± 58 ml/min (P< 0.05)) at both 15% and 25% MVC exercise, respectively. On a separate study day, participants repeated the protocol with a placebo pill (n = 4); there were no differences in any variable between trials 1 and 2 at rest or during exercise. We conclude that acute oral AA is capable of increasing FBF and VO2 during moderate intensity handgrip exercise in older healthy humans.Supported by HL095573
REDUCED FUNCTIONALITY OF RENIN‐ANGIOTENSIN‐ALDOSTERONE SYSTEM IN YOUNG RATS EXPOSED TO HIGH‐SALT DIET
Authors: Crestani Sandra , Garparotto Arquimedes , Marques Maria Consuelo Andrade , Sullivan Jennifer C. , Webb R. Clinton , da Silva Santos Jose Eduardo 
Published: June 2021

High salt (HS) intake is putatively associated with increased incidence and prevalence of hypertension. We hypothesized that HS diet (NaCl at 2, 4 or 8%) given from weaning for 6 weeks would impair the renin‐angiotensin system (RAS). After treatment, animals were anesthetized and the effects of angiotensin I (AI) and II (AII) at 3, 10 and 30 ρmol/kg, or bradykinin (BK; 3, 10 and 30 nmol/kg) on mean arterial pressure (MAP) were evaluated. Blood samples were used to measure the activity of angiotensin converting enzyme (ACE), circulating aldosterone and AII levels. HS intake did not increase MAP, but the responsiveness to AI was increased around 40 and 80% in HS 4 and 8% groups. The plasmatic activity of ACE augmented from 80 ± 2 (control) to 91 ± 3 nmol/min/mlin HS 8% group, while BK‐induced hypotension was reduced. The effects of AII were also increased in HS 8% group. Despite the enhanced ACE activity and responsiveness to exogenous AII, rats exposed to HS intake presented reduced levels of plasmatic AII and aldosterone, suggesting that regulatory changes in RAS system may, at least in young rats, counteract the beginning of hypertension elicited by excessive salt ingestion.Financial support: CAPES, CNPq and NIH.
Substance P‐induced increase in Brain Derived Neurotrophic Factor expression and secretion by intestinal smooth muscle is mediated by a rise in intracellular Ca2+
Authors: Alqudah Mohamamd Abdalkarim , Mahavadi Sunila , Srinivasa Karnam , Grider John 
Published: June 2021

BackgroundWe have previously shown that intestinal longitudinal smooth muscle cells express and secrete brain derived neurotrophic factor (BDNF) and addition of substance P (SP) to cultured smooth muscle cells induces further expression and secretion of BDNF above basal levels. It is not known, however, what cellular signaling pathways mediate SP‐induced expression and secretion of BDNF.AimTo identify the signaling pathways involved in BDNF synthesis and secretion by smooth muscle in response to SP.MethodCultured intestinal smooth muscle cells were treated with 10–100 nM SP for 24 hours in the presence and absence of 1,2 bis (o‐aminophenoxy)ethane‐N,N,N’,N’‐tetraacetic acid (BAPTA) to chelate intracellular Ca2+. BDNF protein expression and secretion were measured by in‐cell western and ELISA, and BDNF mRNA expression was measured by qRT‐PCR.ResultsThe expression of BDNF protein was increased by 10–121% and BDNF secretion was increased by 50% by SP. Consistent with this, BDNF mRNA expression was increased by 161% by SP. Both BDNF protein and mRNA responses to SP were blocked by BAPTA.ConclusionSP stimulation of BDNF expression and secretion requires increased in intracellular Ca2+. The source of the intracellular Ca2+ increased remains to be determined. Supported by grants DK15564 and DK34153 from the National Institutes of Health.
Dysferlin maintains the integrity of transverse tubules and the junctional sarcoplasmic reticulum following contraction‐induced injury
Authors: Roche Joseph A , Resneck Wendy G , Mueller Amber L , Bloch Robert J 
Published: June 2021

BackgroundMutations in the DYSF gene that encodes the protein, dysferlin, lead to human muscular dystrophies known as dysferlinopathies.HypothesisWe tested the hypothesis that dysferlin is present at transverse tubules (TT) and that it helps stabilize TT and their interaction with the junctional sarcoplasmic reticulum (j‐SR) following contraction‐induced injury in vivo.Methods and ResultsThrough improved tissue fixation and antigen unmasking, we found that most of the dysferlin in skeletal muscle is present in a myoplasmic reticulum that flanks Z‐disks in a pattern similar to markers of TT in healthy rat, mouse, and human skeletal muscle. Dysferlin is enriched in TT and SR fractions in sucrose gradients of rat muscle. Injury by large‐strain lengthening contractions increased the labeling intensity of myoplasmic dysferlin in wild type A/WySnJ mouse muscle. At 3hr post‐injury, dysferlin‐null A/J mouse muscle showed disrupted labeling for TT and j‐SR markers in ~75% fibers, whereas only ~20% showed disruption in wild type muscle. By 72hr post‐injury, ~20% and ~2% fibers were necrotic in A/J and A/WySnJ muscle, respectively, and the number of necrotic fibers was reduced 5‐fold in A/J mice treated with the L‐type calcium channel blocker, diltiazem.ConclusionDysferlin plays an important role in protecting TT and the j‐SR from damage following contraction‐induced injury.
Caloric restriction, aerobic exercise or a combination improves metabolic profiles following diet‐induced obesity
Authors: Glynn Erin L , An Jie , Wang Li-Ping , Ilkayeva Olga R , Stevens Robert D , Bain James R , Muehlbauer Michael J , Koves Timothy R , Summers Scott A , Muoio Deborah M , Newgard Christopher B 
Published: June 2021

Diet‐induced obesity (DIO) is associated with several adverse metabolic changes including development of insulin resistance. Aerobic exercise (EX) &/or caloric restriction (CR) can improve many metabolic abnormalities. To examine independent & combined effects of EX & CR on global metabolism after DIO, male Wistar rats were fed a high fat diet (HF, 45%) ad‐libitum for 12 wk, then divided into 4 groups: continued HF diet (HF), 20% CR of HF (CR), ~20% caloric expenditure via EX (EX), or 10% CR + ~10% expenditure via EX (CR+EX). Controls were fed a low fat diet (LF) & samples were collected at 2 & 8 wk. Body weights in CR, EX & CR+EX were lower than LF or HF. Insulin sensitivity was impaired in HF compared to other groups. Preliminary metabolomics analyses show elevated plasma amino acids including leucine/isoleucine, methionine, phenylalanine & tyrosine, & acylcarnitine (AC) species C18:1 & C18:2 at 2 vs 8 wk in EX only. CR, EX or CR+EX often normalized liver AC toward LF values (e.g. C3, C16). DIO rats had lower respiratory exchange ratios (RER) & heat production vs LF, but values were higher in EX & CR+EX vs HF or CR. We conclude CR & EX induce similar improvement in insulin sensitivity but interventions including exercise result in additional changes in the metabolic profile compared to CR alone.Supported by NIH grant PO1‐DK58398 and a grant from the Duke‐NUS, Singapore. E. Glynn was supported by the Jeane B. Kempner Scholar Award Fund.
Chronic administration of a thrombospondin‐1 mimetic: upsetting exercise capacity and the angiogenic balance in skeletal muscle
Authors: Audet Gerald N , Olenich Sara A , Stricker Janelle C , Roberts Kathleen A , Olfert I Mark 
Published: June 2021

Skeletal muscle function is critical in exercise capacity. There is growing evidence that thrombospondin‐1 (TSP‐1), a potent anti‐angiogenic protein, is an important regulator of skeletal muscle function. We tested the hypothesis that chronic exposure to a TSP‐1 mimetic (ABT‐510) would decrease skeletal muscle capillarity and alter the balance between angiogenic proteins. Osmotic minipumps with ABT‐510 were implanted subcutaneously in the sub‐scapular region of C57/BLK6 mice for 14 days. This resulted in a 12% decrease in maximal running speed in the ABT‐510 treated group (P=0.028) with no significant change in the vehicle treated mice. When compared to the vehicle mice, the ABT‐510 group had a 13% decrease in capillarity in the gastrocnemius muscle (GA, P=0.055), 10% decrease in the plantaris muscle (PLT, P=0.051), and a 28% decrease in the soleus muscle (SOL, P<.001). ABT‐510 mice had decreased VEGF in both the GA and SOL muscles (GA; −30%, P=0.016; SOL; −38%, P=0.055), but no change in the PLT. There were no significant differences in endogenous TSP‐1 protein in the GA between groups. These data show that a TSP‐1 mimetic decreases whole body exercise and skeletal muscle capillarity, and alters the balance between VEGF and TSP‐1; and that chronic elevation of the TSP‐1 pathway can directly alter skeletal muscle structure and function.Support: NIH 5T32‐HL090610, AHA 10BGIA3630002.
Exercise‐Induced Angiogenesis, Fiber Size and Muscle Mass Are Reduced in Skeletal Myofiber‐Specific VEGF Gene‐ Deleted Mice
Authors: Delavar Hamid , Tang Kechun , Wagner Peter D. , Breen Ellen C. 
Published: June 2021

Exercise training stimulates angiogenesis in locomotor muscles. We hypothesize that VEGF expressed by skeletal myofibers is necessary for this angiogenic response and muscle hypertrophy. Using a conditional skeletal myofiber‐specific VEGF gene deletion mouse model (HSA‐Cre‐ERT2 X VEGFLoxP), VEGF levels are reduced by >80% in skeletal muscle of adult myofiber VEGF gene‐deleted mice (myoVEGF−/−) compared to control littermates (WT). 3 weeks after tamoxifen‐induced VEGF gene deletion, mice were exercise trained on a treadmill for 8 weeks (1 hr/d, 5d/wk). Capillary density, fiber size and muscle mass were measured in the gastrocnemius, soleus and plantaris. A selective decrease in the capillary/fiber ratio, mean fiber area, and muscle mass were found only in the gastrocnemius.

WT
myoVEGF−/−

Density (Cap./mm2)
Gastroc.
2.83 ± 0.54
1.87 ± 1.1*

Soleus
1.73 ± 0.20
1.39 ± 0.30

Plantaris
1.87 ± 0.23
1.85 ± 0.29

Mean Fiber Area (mm2)
Gastroc.
2830 ± 541
1870 ± 110*

Soleus
1725 ± 203
1387 ± 295

Plantaris
1871 ± 226
1850 ± 290

Cap/Fiber
Gastroc.
1.71 ± 0.18
1.03 ± .11**

Soleus
1.79 ± 0.15
1.65 ± 0.18

Plantaris
1.73 ± 0.22
1.39 ± 0.21

Muscle/Body weight (mg)
Gastroc.
5 ± 0.7
3 ± 0.5*

Soleus
0.6 ± 0.4
0.5 ± 0.4

Plantaris
2 ± 3
0.6 ± 0.1

Significant difference,
p<0.05,
p<0.01

These data suggest VEGF plays a role in regulating exercise‐induced angiogenesis and may be important for muscle hypertrophy and endurance adaptations to training.
Prolonged endurance exercise decreases fiber loss and fiber atrophy in aged male rats
Authors: Barton Gregory P , McKiernan Susan H , Akins Tiffany , Hoffman Marie , Aiken Erik , Martin-Koob Joanne , Aiken Judd , Diffee Gary 
Published: June 2021

Sarcopenia is the age‐related loss of muscle mass and function. Effects of long‐term exercise training on sarcopenia have not been well defined. In this study we assessed skeletal muscle adaptations to prolonged exercise training in rats from late‐middle age to old age. Male rats, 24 mo of age, trained on a treadmill at three levels of intensity: high (HI: 13m/min, 5% incline for 30 min, 5 days per week), moderate (MI: 13m/min, 0% incline for 30 min, 5 days per week), minimally active (MA: 5m/min, for 5 min, 2 days per week) and a sedentary group (S). Rats ran for one year until the rats were age 36 months. The rectus femoris (RF) muscle from 24‐month Controls (C), and 36‐month HI, MI, MA, and S. The RF was weighed, bisected, frozen, sectioned and stained with hematoxylin and eosin. Digital images of RF cross‐sections were used to determine muscle area, fiber number and fiber diameter. Aging significantly reduced muscle mass, muscle area, fiber number and fiber diameter, (24‐month C compared to any of the 36‐month old S, MA, MI or HI). Among the 36‐mo. rats (HI, MI, MA, and S), no differences were observed in muscle mass or muscle area. However, there was a significant increase in fiber number and fiber diameter in all exercise groups (HI, MI, and MA) compared to S. These results indicate that any level of exercise, even minimal levels of activity is capable of decreasing the effects of sarcopenia in aging rats.Supported by NIH AG 030423.
Anti‐Inflammatory Muscle Macrophage Phenotype is Predictive of Resistance Training Gain in Older Individuals
Authors: Lee Jonah Dan , Erfani Rod A. , Campbell Marilyn S. , Mula Jyothi , Peterson Charlotte A. 
Published: June 2021

Macrophages are responsible for phagocytic and reparative functions essential for the initiation and resolution of muscle damage‐induced inflammation. Muscle macrophages are phenotypically characterized by their polarization: either pro‐inflammatory M1 (classic) or anti‐inflammatory M2 (alternative) macrophages. We tested the hypothesis that different polarized macrophages would be associated with muscle adaptability in response to a chronic hypertrophic stimulus in the elderly. M1 and M2 macrophages were quantified from vastus lateralis biopsies in older (n=8; 68.3y) individuals before and after a 12‐week progressive resistance training program. An increase (p<0.05) in the M2, but not (p>0.05) in the M1, macrophage population was observed as an influence of training. Surprisingly, the strength gained in the resistance training program tended to correlate (P=0.065) to the pre‐training amount of M2 macrophages present in resting muscle. In vitro experiments are underway to study the muscle cell‐macrophage interaction directly. Our findings suggest anti‐inflammatory macrophages respond to and also promote a beneficial response to resistance training in aged‐muscle. Therapeutic interventions that affect the balance between muscle macrophage subpopulations may influence the effectiveness of utilizing resistance training as sarcopenia countermeasure.Funding: NIAMS R01AR060701
The response of genes implicated in muscle oxidative metabolism and oxidative stress to acute exercise in COPD
Authors: Slot Ilse , van den Borst Bram , Hellwig Valéry , Kelders Marco , Schols Annemie , Gosker Harry 
Published: June 2021

Skeletal muscle oxidative capacity is impaired and oxidative stress enhanced in COPD, which contributes to muscle dysfunction. We aimed to test the hypothesis that COPD patients have impaired exercise‐induced response of muscle oxidative metabolism‐ and stress‐related genes, especially during exercise‐induced oxygen desaturation.Resting and 4h post‐incremental cycling quadriceps biopsies were obtained from 28 COPD patients and 15 controls. 13 COPD patients desaturated (SaO2 fall ≥4%) and 15 did not. Expression of a broad panel of genes related to oxidative/glycolytic metabolism and oxidative stress were determined by RT‐qPCR.VO2 peak, peak load and produced work were significantly lower in COPD compared to controls, yet most genes responded alike (eg. PGC1α/β, PPRC1, HKII and MnSOD). Notably, HMOX1, implicated in hypoxia and oxidative stress, showed a stronger response in COPD patients, especially in those without desaturation.Although the overall response of metabolic genes to exercise seemed normal in COPD, these responses may actually be relatively greater, since patients did on average 66% less work during incremental cycling. The greater exercise‐induced increase in HMOX1 expression in COPD and the role of oxygen desaturation herein requires further investigation.This research was performed within TI Pharma T1–201.
Impact of TrkB signaling on recovery of phrenic activity after cervical spinal cord injury in rats
Authors: Sieck Gary C , Zhan Wen-Zhi , Mantilla Carlos B 
Published: June 2021

Upper cervical spinal cord injury disrupts descending inspiratory‐related drive to phrenic motoneurons (PMNs) paralyzing the diaphragm muscle (DIAm). There is gradual recovery of rhythmic DIAm activity ipsilateral to injury suggesting strengthened spared synaptic inputs to PMNs. We previously showed that intrathecal treatment with brain‐derived neurotrophic factor (BDNF) enhances recovery of rhythmic DIAm activity after C2 spinal cord hemisection (C2SH). We hypothesized that TrkB signaling in PMN is necessary for functional recovery post‐C2SH. Using a recently validated intrapleural technique, daily injections of TrkB siRNA were administered to adult male Sprague‐Dawley rats. Bilateral DIAm EMG activity was chronically recorded before and after C2SH to assess recovery of rhythmic DIAm activity. In the vehicle‐treated group, functional recovery was evident in ~10% of C2SH rats at 7D and ~40% of rats at 14D post‐injury. In contrast, none of the TrkB siRNA treated rats displayed functional recovery up to 14D post‐C2SH. Transport of intrapleural Cy3‐labeled siRNA was verified in retrogradely‐labeled phrenic motoneurons. Our results indicate that BDNF/TrkB signaling at PMNs is necessary for functional recovery of rhythmic DIAm activity after C2SH.Supported by NIH grant R01 HL096750 and Mayo Clinic
State dependent modulation of breathing in rats during urethane anesthesia
Authors: Pagliardini Silvia , Greer John J , Dickson Clayton T 
Published: June 2021

Breathing is an automatic process that is highly influenced by brain state, with abnormalities occurring more frequently during sleep. Although rodents are commonly used for respiratory neurobiology studies, they show irregular sleep patterns and cycles, which make studies of sleep‐dependent breathing challenging. The objective of this study was to determine if sleep‐like brain state alternations apparent under urethane anesthesia are correlated to changes in breathing parameters and respiratory muscle modulation, and to determine if they mimic changes occurring during natural sleep.Rats were anesthetized and respiratory parameters (rate, minute ventilation and EMG activity in diaphragm, genioglossus, abdominal and facial muscles) were recorded across different brain states as assessed by neocortical and hippocampal EEG. Results were compared with recordings in natural sleep. Our data show that brain state alternations under urethane anesthesia are correlated with changes in breathing rate, variability and respiratory muscle modulation and closely reproduce changes observed in natural sleep. Of particular interest is the present demonstration of prominent state dependent modulation of both genioglossus and abdominal muscle activity, which is a robust feature of sleep and sleep‐like brain state transitions.Supported by CIHR (JJG) and NSERC (CTD). SP is a Parker B. Francis fellow.