bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low salt diet intensifies conducted vasoconstriction via an angiotensin II receptor mediated mechanism
Authors: Riemann Mads , Ngo Anh Thuc , Holstein‐Rathlou Niels‐Henrik , Torp‐Pedersen Christian 
Published: June 2021

ObjectiveOur aim was to investigate 1) the effect of diet sodium content on the potency of conducted vasoconstriction in mouse striated muscle arterioles in vivo, and 2) whether angiotensin II mediates these effects.MethodsKCl was applied locally to induce conducted vasoconstriction in second order arterioles (diameter 36.5±1.6 μm) in the cremaster muscle in anesthetized male C57 mice (n=38). Vasoconstriction was measured locally and upstream from the application site (500 and 1000 μm), using video microscopy. Stimulation was adjusted to 50 % local vasoconstriction in all animals.ResultsAnimals on low sodium diet (0.015%) for 2‐3 weeks exhibited a stronger conduction of vasoconstriction compared to animals on high sodium diet (3%). At 500 μm, the vessel diameter in the low salt group was 47±2.8% of resting diameter and 90±2.1% in the high salt group p<0.01. At 1000 μm, vessel diameter in the low salt group was 63±5.8% versus 95±1.3% in the high salt group p<0.01. These differences were attenuated by the AT1 blocker losartan. Similar but less pronounced results were seen after 6 months on high or low salt diet.ConclusionOur results indicate that conducted vasoconstriction to KCl in mouse cremaster arterioles is intensified by low salt diet, and that this effect is modulated by angiotensin II via AT1 receptors. This phenomenon is seen both after short (2 weeks) and long term (6 months) exposure to the low salt diet.
Hypogonadal Male Runners Do Not Display Endocrine or Performance Decrements during Prolonged Endurance Exercise
Authors: Hew‐Butler Tamara Dawn , Jordaan Esme , Noakes Timothy D , Soldin Steven J , Verbalis Joseph G 
Published: June 2021

Study aims1) determine if hypogonadal male runners exhibit an impaired performance or endocrine response 2) determine which endocrine factors influence testosterone in male runnersDesign58 males participating in ultramarathon plus 2 lab trials with 10 subjectsResultsThe only statistically significant difference in any measured parameter between eugonadal versus hypogonadal men was [androstenedione]p Δ(61.9 vs. 98.9 ng/dl). Statistically significant linear correlations noted between [testosterone]p Δversus: [NT‐proBNP]p Δ(r = 0.41) and [AVP]p Δ(r = ‐0.38). Significant positive correlations noted between age versus: [testosterone]p Δ(r = 0.41) and finish time (r = 0.31) but not pre‐race [testosterone]p . [NTproBNP]pΔ, age, [AVP]pΔ, [cortisol]pΔ, urine osmolality Δand pre‐race [testosterone]p accounted for 68% of the variance noted in post‐race [testosterone]p in nonrecursive pathway diagrams.ConclusionsLow testosterone levels in male marathoners were not associated with decrements in performance or endocrine‐stress response. Collective clusters of endocrine and/or non‐endocrine factors ‐ such as age, BNP, AVP and cortisol ‐ perhaps should be assessed in tandem when considering therapeutic options aimed at male hypogonadism.Research supportAstellas Pharma US, Inc., Deerfield, IL and by Grant M01RR‐023942‐01 from the National Center for Research Resources (NCRR)
A genetic disease in humans demonstrates the importance of hypoxia‐inducible factor in skeletal muscle metabolism
Authors: Formenti Federico , Clarke Kieran , Dorrington Keith L , Edwards Lindsay , Emmanuel Yaso , Lappin Terence RJ , McMullin Mary F , McNamara Christopher J , Mills Wendy , Murphy John A , O'Connor David F , Percy Melanie J , Smith Thomas G , Treacy Marilyn , Robbins Peter A 
Published: June 2021

The transcription factor, hypoxia‐inducible factor (HIF) regulates the expression of a number of metabolic genes. In the recessive condition of Chuvash Polycythemia (CP), the normal degradation of HIF in euoxia is slowed by functional mutation within the von Hippel‐Lindau (VHL) gene. Thus the disease of CP provides an opportunity to understand the role of the HIF‐VHL pathway in metabolic regulation at a systemic level. We recruited 5 CP patients and 5 controls, matched for gender, and similar for age, height and weight (CP vs control: 28±8 vs 32±12 yrs; 1.67±0.1 vs 1.74±0.1 m; 61±6 vs 72±6 kg; mean±s.d.). We measured work rate and lactate during an exercise capacity test on a cycle ergometer, and skeletal muscle magnetic resonance spectroscopy at rest and during light exercise (3, 4 & 5 Watt). Compared with controls, CP patients showed a limited exercise capacity (CP vs control: 2.4±0.9 vs 3.4±0.8 W/kg; p < 0.05), early lactate accumulation, greater phosphocreatine (PCr) depletion (Fig.1) and a greater fall in pH during exercise. We conclude that the VHL‐HIF pathway significantly affects metabolic regulation at a systemic level.Figure 1
The role of central ROS and NO in aldosterone (ALDO)/salt‐induced hypertension
Authors: Xue Baojian , Badaue‐Passos Daniel , Beltz Terry G. , Bhalla Ramesh C. , Hay Meredith , Johnson Alan Kim 
Published: June 2021

It has been shown that increased reactive oxygen species (ROS) production in kidneys and blood vessels contributes to elevated blood pressure (BP) in rats with mineralocorticoid excess. Nitric oxide (NO) also plays an important role in the regulation of ROS production and BP. However, the role of ROS and NO in the brain in the pathophysiology of mineralocorticoid excess is not fully understood. In the present study, we tested the hypothesis that central ROS and NO production is involved in the BP increase produced by ALDO/salt treatment. BP was measured in male and female rats with the use of telemetry implants. Rats were infused with ALDO (0.75 μg/h, 28 days) via an osmotic pump implanted subcutaneously and given access to 1% NaCl as the sole drinking fluid. ICV, but not subcutaneous, infusions of apocynin (4 μg/kg/min) for 28 days attenuated ALDO/salt‐induced hypertension in male rats (central n=3, Δ16.5± 2.3 vs peripheral n=2, Δ30.4 ± 4.1 mmHg). In a parallel study, ICV L‐NAME infusion (50 μg/kg/day) enhanced the pressor effects in ALDO/salt‐treated female rats (n=3, Δ21.7±1.1 mmHg) when compared to ALDO/salt‐treated females with peripheral L‐NAME (n=2, Δ10.6±1.2 mmHg). Central infusions of apocynin alone or of L‐NAME alone had no effect on BP. These results suggest that increased ROS and/or decreased NO in the central nervous system play an important role in the development of ALDO/salt‐induced hypertension.(Support: NIH HL‐59676, HL‐62261, HL‐14388, & DK‐66086)
Adenovirus‐mediated gene transfer of Mn superoxide dismutase to carotid body normalizes enhanced chemoreceptor function in heart failure rabbits
Authors: Ding Yanfeng , Li Yu‐Long , Yin Jingxiang , Zimmerman Matthew C , Schultz Harold C 
Published: June 2021

Peripheral chemoreflex sensitivity is enhanced in both clinical and experimental chronic heart failure (CHF). We have found CuZn superoxide dismutase (SOD) gene transfer to the carotid body (CB) and tempol (an SOD mimetic) reverse the enhanced chemoreceptor function in heart failure rabbits. Here we investigated the role of MnSOD in the enhanced chemoreceptor activity and function of the CB in CHF rabbits. MnSOD protein expression was lower in CHF CB compared with that in sham CBs. Ad MnSOD (1x108 pfu/ml) gene transfer to the CBs significantly increased MnSOD expression in CHF CBs and reduced the baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in the CHF rabbits. Ad MnSOD decreased the baseline single‐fiber discharge from CB chemoreceptors (6.4± 1.3 vs.10.5±0.9 imp/s at ~100 mm Hg PO2) and the response to hypoxia (18.4±2.1 vs. 36.7±2.2 imp/s at ~40 mm Hg PO2, p<0.05) in CHF rabbits. In addition, Ad MnSOD normalized the blunted IK in CB glomus cells from CHF rabbits (362±41 vs. 520±65 pA/pF at +70 mV, p<0.05). Ad MnSOD also normalized the blunted IK induced by angiotensin II in CB glomus cells from sham rabbits. These results suggest that decreased MnSOD in the CB may contribute to the enhanced CB chemoreceptors activity and peripheral chemoreflex function in CHF rabbits.Supported by NIH grant PO‐1 HL 62222
Carbachol injections in the nucleus pontis oralis elicit REM sleep‐like depression of XII nerve activity in the rat in situ perfused working heart‐brainstem preparation (WHBP)
Authors: Brandes Ivo F. , Stettner Georg , Kubin Leszek , Dutschmann Mathias 
Published: June 2021

Patients with obstructive sleep apnea suffer from nocturnal episodes of upper airway collapse and hypoxia that is most severe during rapid‐eye‐movement sleep (REMS). The XII activity is diminished and the upper airway muscle tone is reduced. To study the central neural mechanisms of REMS, in vivo pharmacological models have been used (Kubin, 2001). To test whether upper airway motor tone depression can be also elicited in the in situ rat WHBP, carbachol (25‐50 nl, 10mM) was injected into the pons in n=33 WHBPs while recording XII and phrenic nerve activities (PNA). In 23 preparations, depression of XII nerve activity lasting 16‐24 min occurred within 142 s ± 26. The depressant episodes could be elicited repeatedly by injections at the same site at >30 min intervals. Histological analysis revealed effective injection sites in the nucleus pontis oralis, Bregma ‐8.16 to ‐8.76, (Paxinos and Watson, 2005). Ineffective injection sites were either located in the nucleus pontis caudalis, were too ventral or too lateral. Only carbachol injections into the nucleus pontis oralis trigger REMS like alterations of the breathing pattern in the WHBP.Funded by BCCN Göttingen and HL‐47600.
Sedentary Aging is Associated with a Senescent Endothelial Cell Phenotype that is Ameliorated by Habitual Aerobic Exercise
Authors: Donato Anthony J , Chiang Rhea , Pierce Gary L , Lawson Brooke R , Seals Douglas R 
Published: June 2021

Replicative senescence is used in culture as a model of vascular endothelial aging. However, the relevance to in vivo aging in humans and the influence of lifestyle factors such as habitual exercise are unknown. To gain insight, endothelial cells (EC) were extracted from the brachial arteries of young (YS: n=10; 24±1yr) and older (OS: n=18; 62±1yr) sedentary and older habitually exercising (OE: n=6; 62±1yr) healthy adults. Compared with YS, OS had larger EC size (10,072±317 vs. 9031±306 pxls, P<0.05), greater p53 protein expression (0.57±0.02 vs. 0.45±0.03 p53/HUVEC intensity, P<0.05, quantitative immunofluorescence), a transcription factor related to increased cell senescence, and lower expression of both nuclear hTERT (0.43±0.05 vs. 0.60±0.09 NhTERT/HUVEC intensity, P < 0.05), a measure of telomerase activity, and SIRT‐1 (0.41±0.03 vs. 0.52±0.05 SIRT‐1/ HUVEC intensity, P<0.05), a deacetylase linked to enhanced longevity. EC from OE more closely resembled those from YS, featuring smaller EC size (9075± 309, P<0.05), lower p53 (0.37±0.04, P<0.01) and greater NhTERT (0.60±0.08, P<0.05) vs. OS, although SIRT‐1 expression was not different (P=0.15). Our results indicate that sedentary, but not physically active, aging in humans is associated with development of a senescent vascular EC phenotype. Prevention of vascular endothelial senescence may be an important mechanism by which regular exercise protects against age‐related cardiovascular diseases.NIH AG013038, AG022241, AG006537, AG029337, AG000279, RR00051
Gender‐independent pattern of dyslipidemia and systemic oxidation in overweight children
Authors: Rosa Jaime , Oliver Stacy R , Pontello Andria M , Milne Ginger L , Johnson Sarah J , Sanchez Stephanie C , Flores Rebecca L , Bachmann Georgia V , Galassetti Pietro R 
Published: June 2021

The incidence of pediatric obesity, a major risk factor for cardiovascular disease (CVD) and diabetes, has increased over the past decades. Gender differences in lipid distribution and oxidative status (a key biochemical link between obesity and CVD) are known to exist in the adult population. Little information is available, however, about gender effects on the interaction between oxidative stress and dyslipidemia in children.We therefore measured systemic oxidative stress (F2‐isoprostanes, F2‐IsoP) and lipid variables in 98 male and female peripubertal children (43 normoweight, NW, 13.4±0.5 yrs, 25F, BMI%<85th; 55 overweight, OW, 12.7±2.5 yrs, 25F, BMI%=95th).Overall, OW displayed elevated F2‐IsoP vs. NW (99±7 vs. 74±4, p<0.005) and this pattern was maintained across genders (see figure). OW also displayed alterations of all components of lipid metabolism compared to NW children (FFA 564±46 vs. 372±34, HDL‐C 1.3±0.04 vs. 1.5±0.03, LDL‐C 2.5±0.1 vs. 2.2±0.1, triglycerides 0.95±0.07 vs. 0.53±0.05, all p<0.01); again, as shown in the figure, the pattern of dyslipidemia was similar for both genders.Our data indicate that alterations in lipid metabolism and the consequent increase in oxidative stress occur in obese children in a gender‐independent fashion, likely exposing both genders to a similar degree of increased future risk of diabetes and CVD.Support: NIH grants M01‐RR00827‐28, P01HD048721‐01A1.
Endothelin receptor blockade abolishes angiotensin II sensitivity in intrauterine growth restricted rats
Authors: Ojeda Norma B , Royals Thomas B , Alexander Barbara T 
Published: June 2021

Our laboratory has developed a unique rat model of placental insufficiency that results in intrauterine growth restriction (IUGR), hypertension and an increased responsiveness to angiotensin II (ANG II). We previously demonstrated that activation of the endothelin system contributes to hypertension in IUGR. Therefore, we hypothesize that increased responsiveness to ANG II may be mediated by endothelin in IUGR. Rats were pretreated with RAS blockade (250 mg/L enalapril for 1 week to normalize blood pressure), then systemic and renal hemodynamics parameters were determined before and after acute infusion (30 min) of ANG II (100 ng/kg/min) and endothelin type A receptor blockade (ETRAB), (ABT‐627, 10ng/kg/min). ETARB abolished the increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) and the decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) induced by acute ANG II in IUGR. Thus, these data suggest endothelin may contribute to increased responsiveness to ANG II in IUGR and may serve as an underlying mechanism in IUGR hypertension.* P < 0.05 vs. Control† P < 0.05 vs. Counterpart‡ P < 0.05 vs. Control + ABT‐627
Role of prostaglandins in the loss of lymphatic contractile function in the experimental guinea pig model of TNBS‐induced ileitis
Authors: Rehal Sonia , Roizes Simon , von der Weid Pierre‐Yves 
Published: June 2021

The lymphatic vessel pumping is critical in maintaining tissue fluid homeostasis, particularly during edematous stress, such as inflammation. Loss of this function (i.e. dilated hyporesponsive lymphatic vessels) previously observed during experimental intestinal inflammation could be mediated by prostaglandins, which are heavily involved in the intestinal inflammatory response and potently alter lymphatic contractility. We thus evaluated the ability of lymphatics to synthesize and respond to prostaglandins in physiological and inflammatory conditions.Using real time PCR, we analyzed mesenteric lymphatics, arteries, veins, mesothelium and ileum obtained from control animals, TNBS‐treated guinea pigs and their sham counterpart for the following mRNA transcripts: COX‐1, COX‐2, prostacyclin synthase, prostaglandin E (PGE) synthase 1 and 2, prostacyclin receptor, and PGE2 receptors EP1, EP2, EP3 and EP4. We also measured PGE2 content in lymphatics by ELISA.When compared to sham and control animals, we observed an upregulation of COX‐2 mRNA and a downregulation of PGE synthase 2 and EP4 receptor mRNAs in lymphatics and ileum of TNBS‐treated animals. Preliminary data also showed an increase in PGE2 content in lymphatics from TNBS‐treated animals.Our results further suggest alteration of PGE2 function in lymphatics of TNBS‐treated guinea pigsSupported by the Crohn's and Colitis Foundation of Canada
Blockade of STAT3 does not alter acute injury after hepatic ischemia/reperfusion in mice
Authors: Clarke Callisia Nathelee , Tevar Amit , Edwards Michael , Lentsch Alex B 
Published: June 2021

BackgroundSTAT3 is a critical transcription factor regulating the protective effects of liver ischemic preconditioning. However, its role in hepatic ischemia/reperfusion (I/R) injury is unclear. Here we investigated whether blockade of STAT3 phosphorylation altered the injury response to hepatic I/R injury.MethodsMice were subjected to 90 minutes of hepatic ischemia followed by reperfusion with or without ip injection of 5mg/kg AG490 (selective JAK2 inhibitor) or 10mg/kg of Stattic (direct inhibitor of STAT3 phosphorylation). Mice were sacrificed at 24 hr post reperfusion and liver injury (serum ALT), histology and tissue neutrophil accumulation (liver MPO) measured.ResultsNeither Stattic nor AG490 had any effect on liver injury induced by I/R. However, Stattic significantly reduced neutrophil accumulation.ConclusionThe data suggest that STAT3 is not relevant to acute liver injury after I/R. However, it may be involved in pathways leading to recruitment of neutrophils.
Acute resistance exercise effects on IGF‐1 signaling cascade downstream pathway
Authors: song taejeong , Farrar Roger P 
Published: June 2021

Illuminating muscle hypertrophy mechanisms were main issues for over a decade. Now it is recognized that IGF‐1 downstream pathways are key molecules to increase muscle mass by activating gene transcription, protein synthesis and satellite cell proliferation and differentiation. But the activation timing and patterns of these pathways after resistance exercise is still controversial.The purpose of this study is to investigate the time course and trend of IGF‐1 signaling downstream after acute ladder climbing exercise. Male Sprague‐Dawley rats, 384g, were divided into control (CON), one bout exercised (1B) and three bouts exercised (3B) group and trained once per every three days then sacrificed at 3, 6 and 12 hours after last bout of exercise. Rats were fasted 3 hours before last exercise session and received standardized nutriment supplement via gavage (5m/kg) immediately after the last session.The ratio of FHL muscle mass (mg) to body weight (g) in 3B (1.69±0.1, P < 0.01) is increased significantly comparing to CON (1.49±0.05) and 1B (1.53±0.09). pAkt is peaked at 3B3 (+114%) and both pmTOR (+106%) and pp70S6K (+119%) are the most activated at 1B3. pERK shows peak at 3B12 (+80%). There are no changes of total Akt, mTOR, p70S6K and ERK. These data support that mTOR and p70S6K can be activated independent to AKT and are respond early during training.
Vasopeptidase Inhibitor Improves Coronary Dysfunction in Zucker Obese but not Zucker Diabetic Fatty (ZDF) Rats
Authors: Oltman Christine L. , Kleinschmidt Travis L. , Coppey Lawrence J. , Davidson Eric P. , Yorek Mark A. 
Published: June 2021

Previous studies have shown endothelial dysfunction in coronary and mesenteric near resistance arteries in Zucker obese and ZDF rats. Our hypothesis is that vascular dysfunction is due in part to upreglulation of neutral endopeptidase and treatment with a vasopeptidase inhibitor will improve vascular function. 20‐week‐old Zucker obese and 12‐week‐old ZDF rats were treated with the vasopeptidase inhibitor AVE7688 (500mg/kg) for 12 weeks. Afterwards, coronary and mesenteric function was evaluated using an isolated vessel preparation. Vessels (75 ‐ 175µm intraluminal diameter and ~1 mm in length) were studied under hydrostatic pressure (40mm Hg) and no flow, and internal diameter was measured. Dilator responses were evaluated for acetylcholine (Ach, 10−10‐10−4 M), and calcitonin gene‐related peptide (CGRP, 10−11‐10−9 M) after constriction with U46619.ResultsACh (10μM) responses were attenuated in arteries from untreated rats compared to responses from lean rats (coronary: Zucker obese = 49.4%, ZDF = 50.7% decrease and mesenteric: Zucker obese = 27.4%, ZDF = 33.5% decrease). ACh response was augmented in coronary vessels from AVE7688 treated Zucker obese but not ZDF rats when compared to vessels from untreated rats. Our data suggest that coronary artery endothelial dysfunction is improved when Zucker obese but not ZDF rats were treated with AVE7688. Supported by VA Merits to Dr. Oltman and Dr. Yorek.
Maintenance of contractile properties despite impaired skeletal muscle oxidative metabolism in diet‐induced obesity.
Authors: Shortreed Karin Elizabeth , Krause Matthew P , Huang Julianna H , Dhanani Dili , Ceddia Rolando , Hawke Thomas J 
Published: June 2021

Diet‐induced obesity (DIO) is increasing in prevalence among youth; a time where robust muscle growth occurs. We hypothesized that consumption of a high fat diet (HFD) in early adulthood would negatively impact mouse muscle metabolism and contractile function. HFD (~60% kcal fat for 8 weeks) induced an obese and insulin resistant phenotype with reduced relative muscle mass (72 ± 1.9%) compared to control.Using isolated single muscle fibers for analysis, HFD induced a significant impairment in palmitate and glucose oxidation (72.8 ± 6.6% and 61.8 ± 9.1% of control respectively). This novel technique was validated in intact muscle. Impaired insulin responses were noted for glucose metabolism and glycogen synthesis in HFD muscle vs. control, while glucose and palmitate uptake was not altered between groups. Preliminary RT‐PCR results demonstrate no difference in CPT‐1, PGC‐1α, PPARα or UCP‐2 expression. Further gene and protein analysis into the mechanisms underlying changes in fat uptake and oxidation are currently underway. Despite metabolic impairments, HFD muscle exhibited no loss of maximal contractile force or alteration in fatigue rates.Our data suggest that HFD skeletal muscle is highly adaptive in the face of impaired substrate oxidation, as demonstrated by the preservation of contractile properties. These findings contribute to our understanding of the impact of DIO on developing skeletal muscle.
Phosphorylation of the Tight Junction Protein Occludin on Ser490 Regulates Barrier Function and Contributes to Growth Control
Authors: Runkle E. Aaron , Sundstrom Jeffrey M. , Gonsar Kristin B. , Antonetti David A. 
Published: June 2021

Occludin was the first transmembrane tight junction protein identified but its function remains unclear. Occludin content correlates with barrier properties but gene deletion studies demonstrate it is not essential for formation of tight junctions. Recent data suggest occludin contributes to growth control. Our laboratory has shown that growth factor treatment of vascular endothelial cells alters barrier properties and leads to phosphorylation and redistribution of occludin and occludin Ser490 has been identified as a specific growth factor‐induced phosphorylation site. Here, our goal was to test the hypothesis that occludin Ser490 phosphorylation regulates barrier function in epithelial cells and contributes to control of cell growth. MDCK cell lines that stably overexpress wild type, Ser490 mutated to Ala (S490A) to block or Asp (S490D) to mimic phosphorylation were characterized. Occludin S490D promoted while S490A reduced growth rates as determined by cell count and DNA synthesis. Occludin S490A reduced permeability to 467Da TAMRA and Arg and increased electrical resistance. Finally, in a Ca2+ switch assay, S490A enhanced junction recovery rates while S490D recovered similar to empty vector. These results were further supported using confocal microscopy. Thus, phosphorylation of occludin on Ser490 regulates both barrier function and contributes to growth control in MDCK cells.Supported by grants from NIH 012021 and American Heart Association (AHA) 0815468D.