bluuebunny/crossref_metadata_2025_split huggingface dataset:
δ‐Opioid agonist, [D‐Pen2,5]enkephalin (DPDPE) attenuates the exercise pressor reflex in both freely perfused and ligated rats
Authors: Kim Joyce S , Kaufman Marc P 
Published: June 2021

A reflex, which is elicited by mechanical and metabolic stimuli arising in contracting muscles, is responsible in part for the increases in cardiac output, heart rate, and arterial pressure evoked by exercise. In patients with peripheral artery disease, this reflex is exaggerated and may contribute to their increased risk of adverse cardiovascular events. The afferent arm of this reflex, which is called the exercise pressor reflex (EPR), is comprised of group III and IV afferents. Both μ and δ opioid receptors are expressed on the spinal endings of these afferents which terminate in the dorsal horn of the spinal cord. Evidence suggests that δ‐opioid receptors (DOR) are expressed predominately on the spinal endings of thinly myelinated Aδ fibers (group III), whereas μ‐opioid receptors (MOR) are expressed predominately on the spinal endings of C‐fibers (group IV). Using stimuli that activated group III afferents, namely static contraction, tendon stretch, and lactic acid, we tested the hypothesis that activation of pre and postsynaptic DOR in the dorsal horn attenuated the pressor reflexes in both rats with freely perfused hindlimb muscles and in rats with hindlimb muscles whose arterial supply had been ligated for 72 hours. We activated DOR by intrathecal injection (10μg in 10μl) of the selective δ‐opioid agonist, [DPen2,5] enkephalin (DPDPE).We found that in freely perfused rats, DPDPE significantly attenuated the EPR evoked by static contraction ( n=7; P <0.005) and the muscle mechanoreflex, the latter of which was evoked by stretching the calcaneal tendon (n=9; P <0.05). Likewise, DPDPE attenuated the pressor response to injection of lactic acid into the arterial supply of the hindlimb (n=7; P <0.05). in contrast, DPDPE did no attenuate the pressor response to arterial injection of capsaicin (n=7; P>0.5), which is a more selective stimulus to group IV afferents than it is to group III afferents. In ligated rats, DPDPE attenuated the EPR, the muscle mechanoreflex (both n=6; P<0.05) as well as the pressor response to arterial injection of lactic acid (n=6; P< 0.05). In ligated rats, however, DPDPE did not attenuate the pressor response to capsaicin (n=8; P>0.05). Intrathecal injection of saline (10μl), the vehicle for DPDPE, did not affect the EPR, the muscle mechanoreflex or the pressor responses to lactic acid or capsaicin in either FP or ligated rats. We conclude that activation of δ‐opioid receptors in the dorsal horn attenuates reflexes evoked by group III muscle afferents in both freely perfused and ligated rats.Support or Funding InformationThis work was funded by National Institutes of Health grants R01 AR059397 and P01 HL134609. The NIH is thanked for their support of this work.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endogenous Acetylcholine Limits α1‐Adrenergic Vasoconstriction During Exercise in Humans
Authors: Terwoord Janée D. , Hearon Christopher M. , Richards Jennifer C. , Luckasen Gary J. , Dinenno Frank A. 
Published: June 2021

Sympathetic vasoconstriction is markedly attenuated within the vasculature of contracting compared to quiescent skeletal muscle (“functional sympatholysis”), yet the mechanisms that modulate post‐junctional α‐adrenergic signaling in active muscle remain poorly understood. In rodents, application of the endothelium‐dependent agonist acetylcholine (ACh) blunts sympathetic vasoconstriction in skeletal muscle resistance vessels, and we have recently demonstrated that intra‐arterial administration of ACh enhances functional sympatholysis in humans. Thus, we sought to determine whether endogenous ACh is involved in this integrative control of vascular tone during exercise. In 16 healthy volunteers (8 F, 8 M; 26 ± 1 yrs), we assessed the vasoconstrictor response to intra‐arterial phenylephrine (PE; α1 agonist) at rest and during rhythmic handgrip exercise under control conditions and during local inhibition of muscarinic ACh receptors via intra‐arterial atropine. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) at rest and during 4 min of dynamic handgrip contractions at two exercise intensities (15 and 25% of maximal voluntary contraction, MVC). Adenosine was infused during the resting trials to elevate FBF to levels similar to those observed during exercise. After the vascular response to exercise or adenosine reached steady‐state, we assessed vasoconstriction during infusion of PE for 2 min. The magnitude of sympatholysis was calculated as the percent reduction in vasoconstriction during exercise compared to rest. As expected, the vasoconstrictor response (Δ FVC) to PE was attenuated during exercise at 15 (−20 ± 2%) and 25% MVC (−12 ± 2%) compared with rest (−40 ± 4%; P < 0.05), indicating functional sympatholysis. Atropine did not affect sensitivity to PE at rest (−38 ± 4%; P = 0.60). During 15% MVC exercise, atropine augmented vasoconstriction to PE in women (−25 ± 2 vs. −19 ± 2%, P < 0.05), whereas it did not affect the response in men (−22 ± 2 vs. −22 ± 3%, P = 0.88). During higher intensity exercise, atropine reduced the magnitude of functional sympatholysis by ~50% such that a greater degree of vasoconstriction occurred in response to PE in both women (−22 ± 4 vs. −11 ± 4%, P < 0.05) and men (−22 ± 2 vs. −12 ± 2%, P < 0.05) compared to control conditions. These findings demonstrate that inhibition of muscarinic receptors reduces the ability of contracting muscle to limit sympathetic vasoconstriction in an intensity‐ and sex‐dependent manner, supporting a novel, physiological role for ACh in functional sympatholysis in humans.Support or Funding InformationSupported by HL119337 & HL142240This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High‐Intensity Interval Training and Moderate‐Intensity Continuous Training Improve Endothelial Function Similarly in Adults with Type 2 Diabetes
Authors: Hwang Chueh‐Lung , Lim Jisok , Yoo Jeung‐Ki , Kim Han‐Kyul , Hwang Moon‐Hyon , Handberg Eileen M. , Petersen John W. , Sakarya Yasemin , Holmer Brady J. , Lapierre Stephanie S. , Leey Casella Julio A. , Cusi Kenneth , Christou Demetra D. 
Published: June 2021

Endothelial function is a predictor of cardiovascular disease, the leading cause of death in adults with type 2 diabetes. Aerobic exercise training may preserve or improve endothelial function; however, the optimal exercise prescription remains uncertain. Recently, there has been increasing interest in high‐intensity interval training (HIIT) vs. moderate‐intensity continuous training (MICT). These protocols are most commonly performed on the treadmill which may limit implementation in patients who have lower limb limitations or balance issues. We sought to compare the effect of non‐weight‐bearing all‐extremity HIIT vs. MICT on endothelial function in adults with type 2 diabetes. Forty‐nine sedentary men and postmenopausal women with type 2 diabetes aged 46 to 78 yrs (mean±SE: 63±1 yrs), free of cardiovascular disease, were randomized to HIIT (n=18), MICT (n=16), or non‐exercise control (CONT; n=15). HIIT (4×4‐min intervals at 90% of peak heart rate (HRpeak) interspersed by 3 min recovery bouts at 70% HRpeak) and isocaloric MICT (32 min at 70% of HRpeak) were performed on an Airdyne® all‐extremity ergometer 4 days/week under supervision. Including warm‐up and cool‐down, the total exercise duration per session was 40 min for HIIT and 47 min for MICT. Endothelial function in response to reactive hyperemia was assessed non‐invasively by brachial artery flow‐mediated dilation (FMD) via ultrasonography. Following the 8‐week intervention, FMD increased similarly in HIIT (pre‐ vs. post‐intervention: 3.17±0.62 vs. 4.03±0.71%, P=0.01) and MICT (3.54±0.63 vs. 4.39±0.61%; P=0.02 and P>0.99 for HIIT vs. MICT) while it did not change in CONT (4.02±0.46 vs. 3.74±0.51%, P=0.4). The improvement in FMD was not confounded by changes in brachial baseline diameter, hyperemic shear rate, or systolic and diastolic blood pressure (P≥0.3). In conclusion, all‐extremity HIIT and MICT similarly improve endothelial function in adults with type 2 diabetes which suggests that all‐extremity MICT is an effective alternative for those who are unable or unwilling to engage in all‐extremity HIIT.Support or Funding InformationThis work was supported by National Institute of Aging grant AG050203 to DDC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Duration of Remote Ischemic Preconditioning on the Skin Microvascular Response to Local Heating
Authors: Uridil Audrey I , Kim Jahyun , Lang James A 
Published: June 2021

IntroductionRemote ischemic preconditioning (RIPC), or intermittent periods of ischemia followed by reperfusion, improves endothelial function in conduit vessels; however, whether functional changes occur in the microvasculature is unknown. Using skin as a microvascular model, we hypothesized that the cutaneous vasodilation (VD) response to localized heating would progressively increase with duration of RIPC treatment.MethodsTwelve young adults performed RIPC for two weeks whereas nine completed one week of RIPC. Each RIPC session included 4 repetitions of 5 minutes of arm blood flow occlusion followed by 5 minutes reperfusion. Before and after the RIPC intervention, the skin VD response to localized heating (Tloc = 42°C) was measured using laser speckle contrast imaging (LSCI). Data were normalized to cutaneous vascular conductance (CVC); LSCI flux / mean arterial pressure (MAP).ResultsBaseline CVC and MAP remained unchanged following RIPC (p > 0.05). However, the plateau in the cutaneous VD response to localized heating was augmented after one week of RIPC (Pre: 1.16 ± 0.44, Post: 1.48 ± 0.57 LDF·mmHg−1; p < 0.05) but no further improvement was observed after two weeks of RIPC (Pre: 1.50 ± 0.30, Post: 1.63 ± 0.36 LDF·mmHg−1; p < 0.05). Delta CVC values (post – pre RIPC) were not different between one week and two weeks of RIPC (p = 0.14).DiscussionThese data indicate that repeated bouts of RIPC augments cutaneous microvascular function and suggests that the adaptations with repeated RIPC may have an endothelium‐mediated component. And, longer duration of RIPC did not elicit greater functional changes.Support or Funding InformationIowa Space Grant Consortium (NASA STEM Training Grant) (#134819)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Advanced Glycation End Products in Neutrophil Extracellular Trap Formation
Authors: Cooney Riley , Ahmadi Layla , Petreaca Melissa 
Published: June 2021

During inflammatory responses, innate immune cells such as neutrophils are recruited to the site of infection to fight and kill foreign microbes. Neutrophils eliminate these potential pathogens in three distinct ways: phagocytosis, the generation of toxic reactive oxygen species (ROS), and the production of neutrophil extracellular traps (NETs). NETs, consisting of expelled DNA and associated proteins, bind and capture bacteria, making them easier for neutrophils to kill via ROS and antimicrobial histone functions. In cases involving microbial contamination, inflammation is beneficial and indeed necessary to prevent infection. However, in many disease contexts, inflammation persists despite an absence of pathogens, and the ROS and NETs that otherwise damage and kill pathogens instead damage and kill host tissues. This type of chronic inflammation is often present in Type II diabetics who have persistent high blood glucose levels or hyperglycemia. Hyperglycemia is correlated with neutrophil priming during NET formation and delayed wound healing, suggesting one mechanism linking hyperglycemia with chronic inflammation. However, the mechanisms underpinning hyperglycemia‐induced NET formation remain unclear. Hyperglycemic patients have increased concentrations of advanced glycation end products (AGEs), generated by sugars randomly and irreversibly attaching to the ends of proteins and lipids. AGEs then activate the receptor for advanced glycation end products (RAGE), resulting in pro‐inflammatory signaling that culminates in additional neutrophil recruitment and activation under hyperglycemic conditions. We are investigating whether the increases in NET production when cells are exposed to AGEs before treatment with NET‐inducing stimuli are mediated by RAGE, and found that inhibition of RAGE blocks the AGE‐enhanced, PMA‐induced NET formation in neutrophil‐like HL‐60 cells. Our results supports the therapeutic potential of RAGE inhibitors to reduce NET formation and thereby NET‐associated tissue inflammation and tissue damage in Type II diabetes. We are currently performing experiments to determine whether in normal human polymorphonuclear cells (PMNs), AGE‐enhanced NET production in response to lipopolysaccharide (LPS) is also mediated by RAGE to determine whether AGE‐RAGE interactions prime NET formation in a more physiological system.Support or Funding InformationDePauw University and the Arthur Vining Davis FoundationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Model of Ischemia/Reperfusion Injury in Rat Brain Isolated Mitochondria
Authors: Pille Johannes A. , Salzman Michele M. , Sonju Anna A. , Lotze Felicia P. , Hees Josephine E. , Cleveland William J. , Balzer Claudius , Riess Matthias L. 
Published: June 2021

INTRODUCTIONWhen ischemia occurs, reperfusion is crucial for the survival of the affected tissue. However, the combination of ischemia and reperfusion can cause decreased pH, increased Ca2+, as well as formation of reactive oxygen species (ROS) [e.g., hydrogen peroxide (H2O2)] in the cell, affecting in turn mitochondrial function (e.g., impaired electron transport, ATP synthesis, oxygen consumption). Several of our postconditioning strategies have been found to attenuate ischemia/reperfusion (IR) injury, and to specifically improve mitochondrial function. Yet, it is unclear if the improved mitochondrial function is due to a direct postconditioning effect on mitochondria, or if the improved mitochondrial function is a result of a generally improved cell metabolism. Therefore, to simulate a component of the metabolic stress, namely ROS, occurring to mitochondria during cerebral IR injury, this study focused on injuring rat brain isolated mitochondria by exposing them to H2O2.METHODSMale Sprague‐Dawley rats were euthanized, and their brains removed. Mitochondria were isolated by differential centrifugation and Percoll gradients, then kept on ice to slow their bioenergetics prior to any experimental treatments. To simulate exposure to ROS during ischemia, mitochondria were treated with 200μM H2O2 for 10 min at room temperature (~23°C); controls were kept at room temperature for the same duration. The samples were then diluted ½ with experimental buffer to simulate reperfusion and placed back on ice. ATP synthesis was then measured in a luminometer using a firefly luciferase enzymatic assay. Oxygen consumption was measured by closed cell respirometry with an oxygen meter. In both assays, Complex I and Complex II were examined; Complex I with the substrates glutamate and malate, Complex II with the substrate succinate and the Complex I inhibitor rotenone. Statistics: Data are expressed as mean ± standard error of the mean (SEM). Unpaired 2‐tailed Student's t‐test, α=0.05, * vs control.RESULTSH2O2 treatment significantly impaired mitochondrial ATP synthesis and oxygen consumption for Complex I and oxygen consumption for Complex II (table). However, for Complex II, ATP synthesis did not show a significant difference.CONCLUSIONSThis work shows that the effect of increased ROS (i.e., H2O2) on mitochondrial function, which occurs during IR injury, can be effectively simulated by this model. Future work will utilize this model to test whether our post conditioning strategies work directly on mitochondria during IR injury.Support or Funding InformationThis work was supported by institutional funds, NIH grant (5R01 HL123227), and a Merit Review Award (I01 BX003482) from the U.S. Department of Veterans Affairs Biomedical Laboratory R&D Service.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glutathione Potential and Levels of Hydrogen Peroxide in Vulnerable Parkin Loss‐of‐Function Drosophila Neurons
Authors: Keoseyan Petros Peter 
Published: June 2021

Parkinson's Disease is a neurodegenerative disorder brought on by the loss of cells in the substantia nigra pars compacta (SNpc).1 The mechanism of selective neurodegeneration in this region is yet to be elucidated. A small subset of PD patients inherits a disease‐causing mutation of the PRKN gene which encodes for parkin. The inheritance of homozygous PRKN mutations and subsequent expression of the dysfunctional parkin protein is thought to result in decreased mitochondrial protein turnover.2 Decreased turnover of damaged mitochondrial proteins could result in decreased mitochondrial respiration and increased reactive oxygen species (ROS) production. Indeed, parkin loss‐of‐function patient samples and models exhibit increased levels of reactive oxygen species (ROS).3We have previously reported a selective increase in mitochondrial protein oxidation in degenerating dopaminergic neurons in parkin null Drosophila. We hypothesize that this results from increased hydrogen peroxide (H2O2) levels and/or decreased glutathione redox potential (EGSH).4To determine relative H2O2and EGSH, we measured total volumes of mitochondrially‐targeted redox‐sensitive GFP (roGFP) when it is fused to yeast oxygen receptor peroxidase 1 (orp1) or human glutaredoxin 1 (grx1) in the protocerebral posterior lateral 1 (PPL1) dopaminergic cluster. The maximum excitation wavelength of roGFP shifts from 488 to 405 nm when oxidized. By measuring the volume ratios of roGFP0‐orp1 and roGFP0‐grx1 excited by 405 nm over those excited by 488 nm, we can determine relative levels of H2O2 and EGSH, respectively.We demonstrated that parkin loss causes increases in H2O2 levels and (EGSH) in Drosophila dopaminergic neurons that are homologous to the mammalian SNpc. Our data suggest that increased H2O2levels contribute to mitochondrial protein oxidation and that decreased glutathione activity does not seem to be implicated. Strategies aimed at reducing H2O2 levels or increasing antioxidant activity may buffer the effects of decreased mitochondrial protein turnover caused by parkin loss of function.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Does the Synthetic Corticosteroid, Prednisolone, Impact the Insulin‐Like Growth‐Factor Binding Protein (igfbp) Network of Atlantic Salmon Parr?
Authors: Chang Annaliese , Kalinowski Matthew , McCormick Stephen , Kelly John , Breves Jason 
Published: June 2021

The growth performance of teleost fishes is largely controlled by the growth hormone (Gh)/insulin‐like growth‐factor (Igf) system. Furthermore, Igfs interact with an expanded suite of cognate binding proteins, termed Igf binding proteins (Igfbps), produced by key metabolic tissues such as liver and muscle. Igfbps modulate the biological activities of Igfs under various physiological situations, such as when a glucocorticoid stress response has been mounted. In juvenile Atlantic salmon (Salmo salar), we have previously identified two igfbp genes, namely igfbp1b1 and igfbp1b2, that increase their expression in response to the endogenous glucocorticoid cortisol. These responses underlie, in part, the inhibition of anabolic processes known to occur in parallel with a glucocorticoid stress response. In the current study, we tested the hypothesis that the synthetic corticosteroid, prednisolone, may similarly inhibit anabolic processes by impacting the Gh/Igf/Igfbp network. We implanted Atlantic salmon parr with prednisolone (0, 2.5 and 25 μg/g body weight) or cortisol (25 μg/g) and sampled individuals after 14 days. We observed reduced growth rates (fork length) following treatment with the high dose of prednisolone (25 μg/g) and cortisol. We will report igfbp transcript levels in liver and skeletal muscle to resolve whether activities within the Igfbp network are modulated by prednisolone in juvenile Atlantic salmon.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of blocking muscarinic receptors using atropine on thyroarytenoid muscle recruitment during swallow and breathing
Authors: Mian Seema , Huff Alyssa D , Reed Mitchell D , Iceman Kimberly , Pitts Teresa 
Published: June 2021

Atropine, a muscarinic acetylcholine receptor antagonist, is a commonly used drug to reduce mucous production during surgery. Because atropine blocks the parasympathetic action of acetylcholine, atropine may modulate the balance of parasympathetic and sympathetic activity. In jaw muscles, increased sympathetic drive decreases muscle contractility and reduces muscle spindle feedback. There is evidence for sympathetic innervation of laryngeal muscles, however, few studies have investigated the effects of changing sympathetic drive to laryngeal muscle recruitment during specific behaviors. As such we hypothesized that blocking parasympathetic activation would attenuate laryngeal muscle drive during swallow and breathing. To investigate, we blocked muscarinic receptors via IV infusion of atropine in a dose dependent manner (0.02, 0.07, 0.2, 0.7, 2.0, 7.0 mg/kg). Using steel wire electrodes, bipolar electromyography (EMG) recordings were made in upper airway muscles (mylohyoid, geniohyoid, thyroarytenoid and thyropharyngeus) and the costal diaphragm in Sprague Dawley rats. Swallow was induced by administering 1cc of water into the oral pharynx via syringe. Duration and amplitude of thyroarytenoid (ThAr) activity was measured during breathing and swallow for each concentration of atropine. There was a differential effect of thyroarytenoid EMG activity with a significant reduction during swallow with no change in drive during breathing. Additionally, there was no significant change in number of elicited swallows. These results suggest attenuation of parasympathetic activity on laryngeal muscles may differentially change motor recruitment during specific behaviors such as swallow and breathing.Support or Funding InformationThis work was supported by NIH grants HL 111215, HL 103415 and OT20D001983, the Craig F. Neilson Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.