bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular, autonomic, and thermoregulatory effects of repeated exertional heat stress in rats
Authors: Stauss Harald M , Choudhary Navita , Nash Abigail , Liaboe Frederick O , Kregel Kevin C 
Published: June 2021

A single bout of exercise in the heat (ExHS) produces specific alterations in autonomic function. This study aimed to investigate the effects of multiple bouts of ExHS (10 ExHS bouts over 5 days; 2x/day). Rats (n=8) were run on a motorized running wheel (7–11 m/min) at 39°C until core temperature (Tc) reached 41.8°C. Blood pressure (BP), heart rate (HR) and Tc were recorded telemetrically for 3 days before, during, and 3 days after the ExHS protocol. Both low frequency (LF) HR variability (HRLF) and LF systolic BP (SBP) variability (SBPLF) increased from baseline values in the night following the first protocol day and remained elevated during the nights following the remaining 4 days of ExHS. Compared to baseline (and controls), HR and Tc were temporarily elevated in the night following the first protocol day (368±11 vs. 317±4 bpm and 38.8±0.04 vs. 37.7±0.08°C) but returned to baseline in the night following the fifth protocol day, suggesting a training and heat acclimation effect. HR‐related measures suggested no changes in cardiac parasympathetic modulation occurred with ExHS. The elevated nocturnal HRLF and SBPLF throughout the ExHS protocol, together with the blunted HR and Tc responses at the end of the ExHS protocol, suggest that chronic exposure to ExHS can lead to a sustained increase in cardiac and vascular sympathetic activity despite training and heat acclimation.Supported by DoD/USAMRMC #W81XWH‐10‐2‐0115.
Comparison of internal temperature responses to prolonged arm and leg ergometer exercise
Authors: Keller David M , Samels Mitchel R , Butts Cory L 
Published: June 2021

Understanding thermoregulatory responses to different modes of exercise has important implications from both experimental and spaceflight‐countermeasure perspectives. It is unknown whether prolonged, dynamic arm or leg exercise at the same metabolic demand (i.e., VO2) will elicit similar internal temperature (Tcore) responses. Six subjects (N=6) completed separate, 60 minute trials of Arm and Leg cycle ergometry. Heart rate (HR), mean arterial pressure (MAP) and Tcore (via pill telemetry) were measured throughout exercise. The exercise workload was determined as follows: Watts = 0.35·Body Mass (kg). The VO2 responses to Arm (10.2±0.5) and Leg (9.9±0.6 ml/kg/min) exercise were not different (p = 0.4). However, HR responses were greater during Arm cycling (87±7) compared to Leg cycling (78±4 bpm) at minute 60 (mode*time interaction, p<0.01). MAP responses only tended to be different between Arm and Leg cycling (p=0.051). Interestingly, Tcore responses were greater during Arm cycling at minutes 40, 50 and 60 (mode*time interaction, p<0.01). Although the greater Tcore responses to Arm exercise were modest (difference of means ~0.1 °C), they are supportive of differences between exercise modes that may be of physiological relevance at both greater exercise intensities and during repeated exercise exposure (e.g., heat acclimation).Support by NASA Grant NNX08AY40G
Animal Model of Simulated Microgravity: A comparative study of hindlimb unloading via tail vs. pelvic suspension
Authors: Chowdhury Parimal , Long Ashley , Harris Gabriella , Soulsby Michael , Akel Nisreen , Gaddy Dana , Jayroe John , Dobretsov Maxim 
Published: June 2021

The aim of this study is to compare the effects of simulated microgravity in tail suspended (TS) as well as in pelvic suspended (PS) rats mimicking aspects of prolonged bed rest and sub‐clinical insulinopenia.Materials and MethodsAdult male Sprague‐Dawley rats divided into suspended and control‐non‐suspended groups (6 each per group), were subjected to two separate methods of suspension and maintained with regular food and water for two weeks. Body weights, food and water consumption, soleus muscle weights, malodialdehyde levels of soleus muscle and brain tissues were measured. Pressure‐pain threshold (PPT) was measured using Randall‐Selitto technique at regular 2–3 days intervals during one week before and 2 weeks after HLS.ResultsBody weights in suspended rats from day 10 are significantly different between groups. Food and water intakes are not different between control and suspended groups. Suspended rats had smaller soleus muscle weights and increased MDA levels (p <0.05). PPT were decreased below control after 5 days of PS and 10 days of TS and continued to drop till day 14. X‐ray images show less spinal deformity in PS rats as compared to TS rats.ConclusionsThese data suggest that both procedures develop peripheral neuropathy. Pelvic suspension appears to provide a suitable alternative to tail suspension for chronic hindlimb unloading alleviating excess stress.
Reduced translocation of the TRPv1 receptor in afferent neurons of cardiomyopathic rats
Authors: Nguyen Minh M , Stout Laurence E , Li Qinglu , Garry Mary G 
Published: June 2021

Heart failure (HF) patients exhibit an abnormal exercise pressor reflex (EPR) in response to exercise. Previous studies have implicated the TrpV1 receptor, a vanilloid receptor and transmembrane ion channel, as a mediator of the EPR. A necessary step in activation of TRPv1 is translocation to the membrane. To determine if the translocation of TRPv1 is affected in HF, we compared the subcellular localization of TRPv1 in primary cultures of dorsal root ganglia (DRG) from normal and cardiomyopathic rats. DRGs (L4–L6) of normal or cardiomyopathic rats were evaluated in the presence or absence of NGF. Cells were stained for TrpV1 and fluorescence intensities of membrane and cytoplasm were quantified. Normal NGF treated DRG cells showed an increased ratio of membrane to cytoplasmic TrpV1 staining as compared to normal untreated control. In HF, the ratio of membrane to cytoplasmic TrpV1 was similar regardless of treatment. These results suggest that HF DRGs are impaired in their ability to recruit TrpV1 to the membrane. Furthermore, this suggests that abnormal EPR response in HF patients may be due, in part, to decreased TrpV1 activity due to reduced TrpV1 membrane localization.Studies supported by: NIH 2R01HL070242‐07A2 (MGG).
Inhibitor of complement activation attenuates placental ischemia‐induced hypertension in rat
Authors: Lillegard Kathryn E , Johnson Alex C , Lojovich Sarah J , Bauer Ashley J , Marsh Henry , Gilbert Jeffrey S , Regal Jean F 
Published: June 2021

Preeclampsia is characterized by compromised placental perfusion and new onset hypertension during pregnancy. The complement system is part of the innate immune system and complement activation is known to increase in preeclampsia.HypothesisComplement activation is critical for placental ischemia‐induced hypertension. To test the hypothesis, we used the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia to induce hypertension and determined the effect of inhibiting complement activation using a recombinant soluble form of an endogenous complement regulator, soluble complement receptor‐1 (sCR1; CDX‐1135). On gestation day 14 (term = 21 d) rats underwent sham surgery or clips were placed on the inferior abdominal aorta and ovarian arteries to create RUPP. RUPP and Sham animals received 15 mg/kg sCR1 or saline (Veh) on days 14–18 and mean arterial pressure (MAP) was measured day 19 via arterial catheter. Circulating complement component 3 decreased in RUPP vs Sham (p<0.05) suggesting the component had been cleaved and complement activation had occurred. MAP increased in RUPP‐Veh rats compared to Sham‐Veh rats (109 ± 3 vs 95 ± 3 mmHg), and sCR1 treatment significantly attenuated the increase in MAP in RUPP rats (99 ± 3 mmHg, p<0.05). Thus, inhibition of complement activation may be a viable treatment for hypertension in preeclampsia. Support: Univ Minn Grant‐in‐Aid & NIH HL109843.
Early life stress induces endothelial dysfunction in a mouse model of maternal separation
Authors: Ho Dao H. , Yu Megan L. , Bazacliu Catalina , Pollock Jennifer S. 
Published: June 2021

Early life stress (ELS) is linked to cardiovascular disease in adulthood. We used a mouse model of maternal separation with early weaning (MSEW) to study ELS‐mediated adult cardiovascular pathology. We hypothesized that MSEW induces vascular dysfunction, and sensitizes adult male C57BL/6 mouse to vasoactive factors. MSEW litters were subjected to maternal separation 4h/day (postnatal days (PD) 2–5) and 8h/day (PD6‐16), and weaned at PD17. Control litters were undisturbed until weaning at PD21. We performed wire myography on thoracic aortas of 12‐week‐old mice. MSEW blunted maximum acetylcholine‐induced vasorelaxation (49.8±30.8% vs 72.2±18.4%, p=0.02). Pretreatment (20 min) with apocynin (300μM) and superoxide dismutase (PEG‐SOD, 100 units/ml) reversed this effect. Sodium nitroprusside‐induced vasorelaxation was unaltered by MSEW. Aortas from MSEW mice were hyper‐responsive to phenylephrine‐induced vasoconstriction (61.9±27.0% KCl vs 38.6±18.9% KCl, p=0.04). Baseline SBP (tail‐cuff plethysmography) of MSEW mice was not different from control (109.3±10.9 vs 116.7±20.8mmHg, respectively). Chronic infusion of norepinephrine (7.6μg/kg/min) led to an attenuated hypertensive response in MSEW mice (p≤0.001, main effect). ELS induces classical endothelial dysfunction through an NADPH oxidase‐mediated increase in reactive oxygen species, and a pathological vascular phenotype.PO1 HL 69999
Stimulation of renal sodium transporters’ abundance and phosphorylation during chronic angiotensin II (AII) infusion requires intrarenal AII formation
Authors: Fletcher Nicholas Keech , McDonough Alicia Ann , Nguyen Mien T.X. , Janjulia Tea , Bernstein Kenneth E. , Gonzalez-Villalobos Romer A. 
Published: June 2021

The hypertensive response to AII infusion (400ng/kg/min for 14 d) is blunted in mice expressing normal systemic ACE levels but no kidney ACE (ACE 10/10) vs. WT mice: mean arterial pressure increased 28 mmHg in ACE 10/10 mice vs. 42 mmHg in WT mice (p<0.001). Kidney AII content was also reduced 50% in AII infused ACE 10/10 vs. WT (p<0.05), (Gonzalez‐Villalobos, 2011). We tested the hypothesis that the reduced hypertensive response to AII infusion in the ACE 10/10 mice was due to blunted increases in renal Na+ transporters’ abundance or phosphorylation (‐P) along the nephron. Na+ transporter abundance was measured in whole kidney homogenates by immunoblotting. Density values in AII infused mice were normalized to values in uninfused WT and ACE10/10 mice defined as 1.00.

Sodium Transporters
AII infused WT
AII infused ACE 10/10

NHE3
1.03 ± .06
0.76 ± .11

NHE3‐P
0.99 ± .06
0.70 ± .02

NKCC
0.86 ± .03*
0.97 ± .03

NKCC‐P
2.87 ± .38*
1.01 ± .22

NCC
1.61 ± .15*
0.94 ± .10

NCC‐PS71
2.24 ± .91*
1.01 ± .29

β ENaC
0.93 ± .02
0.96 ± .07

p< 0.05 AII vs. uninfused.

Conclusions1) In WT, AII infusion significantly increases NCC, NCC‐P, NCC‐P/total, NKCC‐P, and NKCC‐P/total which may account for the hypertension. 2) In ACE 10/10, lacking intrarenal ACE, AII did not provoke any of these responses indicating that the increased abundance and –P of transporters, like the rise in BP, are dependent on AII stimulation of intrarenal RAS. DK0837854, R00DK083455‐03
Leishmania infantum ZIP3 is a zinc transporter that is tightly regulated by zinc status
Authors: Carvalho Sandra , Silva Rosa , Shawki Ali , Mackenzie Bryan , Castro Helena , Eide David , Costa Vítor , Tomás Ana M 
Published: June 2021

The ZIP family comprises proteins involved in transport of divalent metals in many organisms. Among three putative ZIP members in L. infantum, we have identified LiZIP3 as a protein involved in the acquisition of zinc since (1) expression of LiZIP3 in a yeast strain defective in zinc acquisition systems rescued the growth in zinc‐limiting medium and (2) expression of LiZIP3 in Xenopus laevis oocytes modestly stimulated the uptake of 65Zn2+.In L. infantum, LiZIP3 expression was induced in the presence of the metal chelator EDTA and decreased following the addition of zinc. Furthermore, we found that, whereas the protein was present at the surface of the parasite under zinc‐limiting conditions, LiZIP3 level decreased after 24 hours of zinc supplementation and membrane localization was lost. LiZIP3 mRNA levels increased when parasites were grown in low‐zinc medium and decreased within one hour following zinc addition, indicating that regulation of LiZIP3 expression is mediated largely at the level of mRNA stability. We observed no LiZIP3 mRNA down‐regulation in response to zinc when we inhibited protein synthesis, implicating a labile protein in the destabilization of the mRNA when zinc is available.Together, our data suggest that LiZIP3 is a zinc transporter ‐ the first identified in Leishmania ‐ and that its expression is tightly regulated by zinc status.Financial support – FCT, NIDDK, Univ. Cincinnati, NCI
Effects of noble gas conditioning on Caveolin expression in the rat heart in vivo
Authors: Weber Nina Claudia , van de Vondervoort Djai , Niesman Ingrid R. , Saldana Michelle , Roth David M. , Preckel Benedikt , Patel Hemal H. 
Published: June 2021

Caveolins are structural scaffolding proteins that allow for organization of signalling molecules in caveolae, membrane invaginations enriched in lipids. Caveolin‐3 (Cav‐3) is a heart specific isoform that is modulated by volatile anesthetics and is required for cardiac protection. We hypothesized that the cardioprotective noble gases Helium (He) and Xenon (Xe) also influence the enrichment of Cav‐3 to caveolae in vivo. Sprague‐ Dawley rats underwent 25 minutes of myocardial ischemia and 2 hours of reperfusion. Rats where left untreated (Con) or underwent different preconditioning (PC) protocols: in He late PC (HeLPC), rats inhaled He for 3×5 min a day before the experiment, the He postconditioning (HePost) group inhaled 70% He for 15 min at the onset of reperfusion. The Xe‐PC rats inhaled 70% Xe for 3×5 min before ischemia. Hearts were processed for sucrose density gradient centrifugation to purify caveolae. Cav‐3 and 1 expression were determined by immunoblotting. HeLPC and HePost increased Cav‐3 localization from 0.2±0.1 in Con to 0.4±0.1 and 0.4±0.2 (arbitrary units), respectively, in buoyant caveolar fractions indicative of increased caveolae formation. Xe‐PC had no effect on Cav‐3 localization. We found no effect on Cav‐1 localization.These data suggest that He might exert its cardioprotective effect by augmenting Cav‐3 localization to caveolae to further enhance cardioprotective signaling.
Impact of rosiglitazone and metformin on serum pro‐inflammatory molecules and adipocytokines in rats with chronic fructose diet
Authors: Sigrist-Flores Santiago , Pardo Juan Pablo , Murguía-Romero Miguel , Villalobos-Molina Rafael , Jimenez-Flores Rafael 
Published: June 2021

Metabolic syndrome is a pathological condition involving metabolic abnormalities: abdominal obesity, hyperinsulinemia, dyslipidemia, impaired glucose uptake, all of them linked with increased risk for DM2, and CVD. Those alterations are closely related to a chronic inflammation promoting endothelial dysfunction, and other reactants of acute and chronic phases. Adipose tissue produces adipokines that integrate endocrine, autocrine and paracrine signals, contributing to inflammation. We aimed to explore the in vivo effect of metformin and rosiglitazone in fructose‐fed rats.We evaluated sICAM‐1, TNF‐α, IL‐6, IL‐1β, C‐Reactive Protein, leptin, adiponectin, and glucose, triglycerides, uric acid, HDL‐C and LDL‐C. Drugs were administered alone or combined for 3 mo, in rats fed 30% fructose for 4 mo. At month 6 with fructose diet, altered glucose, triglycerides and uric acid, were observed. Fructose induced changes in IL‐6 and IL‐1β at month 7, not observed in rats treated with metformin. Combined therapy decreased weight and normalized leptin and IL‐1β. Thus, increase in IL‐6 and IL‐1β after fructose intake, evidence inflammation, normalized by the combined effect of metformin and rosiglitazone, and harmonizes with decreased leptin and weight loss.Supported in part by grant PICDS08‐69 from ICyT‐G.D.F., México.
THE EVALUATION OF BONE PROTEOME OF PALM VITAMIN E‐SUPPLEMENTATION IN OVARIECTOMISED RATS
Authors: Okechukwu Nwabueze Patrick , Mohamed Norazlina , Soelaiman Ima Nirwana , Shuid Ahmad Nazrun , Muhammad Norliza 
Published: June 2021

IntroductionOsteoporosis is a common disease characterized by decreased bone mineral density (BMD) and microarchitectural deterioration of bone structure. Supplementation of palm vitamin E for 10 months was able to prevent loss of bone density in ovariectomised female rats. The mechanism by which palm vitamin E exerts these effects is still unknown. One study has found that some proteins were overexpressed in the ovariectomised rats as opposed to the control rats.ObjectiveWe hypothesized that palm vitamin E may act by preventing the protein expression changes.MethodThe study was divided into five groups; ovaritectomised treated with Palm vitamin E, Olive oil, alpha tocopherol, sham and normal. Femoral bones were harvested for protein extraction. Two‐dimentional gel electrophoresis was performed and proteins were analyzed using software genomic solutions Investigator.Result and DiscussionDifferential protein expression profile reveals that about five (5) protein spots were overexpressed in ovariectomised group treated with olive oil compared the ovariectomised group treated with palm vitamin E. While about three (3) protein spots were not expressed in the ovariectomised group treated with olive oil and were expressed in the group treated with palm vitamin E. The differential protein expression may account for the mechanism through which palm vitamin E exert its anti‐osteoporotic effect. However more research is ongoing to identify the proteins of interest.
Fetal Endothelial Colony Forming Cells Assist Vasculogenesis in the Pregnant Uterus
Authors: Sipos Peter , Rens Willem , Schlecht Helene , Fan Xiaho , Wareing Mark , Baker Philip , Davidge Sandra , Crocker Ian 
Published: June 2021

Endothelial Colony Forming Cells (ECFCs) are more robust in the fetus than adult. Uterine blood flow increases in pregnancy, triggering expansion of the uterine vasculature. Fetal ECFCs may contribute to these adaptive requirements.(i) Fluorescent fetal‐derived cells were tracked in uteri in native female mice mated with eGFP‐expressing males. (ii) Human fetal eGFP‐expressing ECFCs were tracked in uteri of pregnant NOD/SCID mice, whose fetuses had been transplanted with these cells by in vivo intracardiac injection. (iii) In human uterine microvessels of mothers with male offspring, SRY gene was quantified by RT‐QPCR and (iv) Y‐chromosome hybridised in‐situ to localise fetal cells.(i) Fetal endothelial‐like cells were identified in murine uterine vessels (n=7). (ii) Transplanted human ECFCs (n=8) integrated into the uterine endothelium. (iii) RT‐QPCR detected SRY in 50% of human uterine vessels (n=12). The number of copies corresponded to 246±45 fetal cells/mm2 maternal endothelium (≈10% vessel wall). (iv) Fetal cells were observed in the human uterine endothelium (n=4).These data suggest that fetal ECFCs assist the vasculogenesis of the pregnant uterus and potentially vascular repair in the mother.
Pentoxifylline reduces myocardial oxidative stress induced by exposure to tobacco smoke
Authors: Azevedo Paula Schmidt , Polegato Bertha , Portugal Priscila , Batista Diego , Lustosa Beatriz , Rafacho Bruna , Oliveira Fernando , Mascoli Alexander , Roscani Meliza , Fernandes Ana Angélica , Zornoff Leonardo , Paiva Sergio , Matsubara Luiz , Pereira Elenize , Minicucci Marcos 
Published: June 2021

The objective of this study is to evaluate the role of pentoxifylline (P) in heart remodeling induced by exposure to tobacco smoke (ETS).MethodsWistar rats were allocated in 4 groups: C (control); S (smoke); P (diet with P 100mg/kg) SP (smoke + diet with P100mg/kg). After 2 months, animals were submitted to echocardiography, isolated heart study, and oxidative stress evaluation. Two way anova and Holm Sidak tests were performed.ResultsETS leaded to an increase in left atrium area (p=0,04) and in left ventricle weight (p=0,04) and to impairment of ventricle function that was improved by pentoxifylline as observed in maximum positive derivative (C=3851±245; P=3500±400; S=2725±310; SP=3950± 310) (p=0,01). ETS increased oxidative stress that was attenuated by pentoxifylline: lipoperoxides (C=133,4±14,7; S=175,8±11,5; P=100,0±14,5; SP=128,3±11,9) (p<0,001), Glutathione peroxidases (C=37,4±4,8; S=17,519±3,9; P=33,6±6,4; SP=37,2±5,3) (p<0,001), superoxide dismutase (C=19,4±1,9; S=11,2±0,89; P=16,4±1,6; SP=21,7±2,9) (p<0,001).ConclusionIt is possible that pentoxifylline attenuates cardiac remodeling induced by ETS, in part due to reduction of oxidative stress.
The identification of gene clusters that correlate with vascular adaptations after physical deconditioning and exercise training in humans
Authors: Lammers Gerwen , van Duijnhoven Noortje T. L. , Hoenderop Joost G. , Horstman Astrid M.H. , de Haan Arnold , Janssen Thomas W.J. , de Graaf Mark , Pardoel Elisabeth M. , Verwiel Eugène T.P. , Thijssen Dick H.J. , Hopman Maria T.E. 
Published: June 2021

Physical inactivity and exercise training result in opposite adaptations of vascular structure, but the molecular mechanisms behind these adaptations are not completely understood. Therefore, this study examined both vascular characteristics of the superficial femoral artery (using ultrasound) and gene expression levels (from a muscle biopsy). First, we compared able‐bodied controls (n=6) with spinal cord‐injured (SCI) individuals (n=8) to assess the effects of long‐term deconditioning. Able‐bodied controls were also examined before and after short‐term deconditioning using 3 weeks of unilateral limb suspension (ULLS). SCI individuals received 6 weeks functional electrical stimulation (FES) exercise training. Baseline diameter and hyperaemic flow were lower after deconditioning and improved after training, whilst intima‐media thickness/lumen ratio was higher after deconditioning and decreased by training. Gene clusters including the vascular endothelial growth factor (VEGF) pathway (Figure), transforming growth factor beta 1 (TGFB1), and extracellular matrix (ECM) components strongly related with these vascular adaptations. Thus, this approach resulted in the identification of genes that may be involved in structural vascular adaptations after physical (in)activity.GL was funded by Gelderland‐Overijssel‐EFRO, NTLvD by the Netherlands Heart Foundation, and JGH by the EURYI award.