bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Anoxic Reduction of Mitochondrial ROS Production Leads to Increased GABAergic Interneuron Activity and Electrical Suppression in Turtle Cerebral Cortex
Authors: Hawrysh Peter , Hogg David , Buck Les 
Published: November 2023

The anoxia‐tolerant western painted turtle (Chrysemys picta bellii) has uniquely adapted to surviving extended periods of low O2 by reducing the activity of energy‐consuming pathways. The largest such pathway is the re‐establishment of neuronal ionic gradients following excitatory transmission. We hypothesize that the mitochondria serve as the initiator of neuronal silencing by sensing changes in O2 and triggering increased GABA release with the goal of reducing overall energetic demand. Here, we show that the reduction of mitochondrial O2 consumption during anoxia limits the production of reactive oxygen species (ROS), as evidenced by a fluorescence reduction of the ROS‐sensitive dye DCF during anoxia. Whole‐cell patch clamp recordings demonstrate that this reduction in ROS enhances both tonic and phasic post‐synaptic GABAA receptor currents. To determine how the reduction in ROS affects GABA release, we first determined the location of neurons that produce and release GABA. Fast‐spiking GABA‐releasing stellate interneurons were found to sparsely reside in the molecular and subcellular layers of the turtle cortex, based in immunohistochemical staining for glutamate decarboxylase and the voltage‐sensitive K+ channel subunit Kv3.1. These neurons fire action potential bursts at a frequency of 0.09 ± 0.01 Hz, which is the same frequency that GABAergic phasic currents occur in pyramidal neurons. Following the transition to anoxia or during pharmacological ROS scavenging with N‐acetylcysteine, stellate interneurons depolarize and become more excitable, as evidenced by the increased prevalence of action potentials between and during bursts. These results suggest that mitochondrial ROS signaling in stellate interneurons controls widespread GABAergic signaling in the turtle cortex.Support or Funding InformationResearch was supported by an Ontario Graduate Scholarship to Peter Hawrysh and a Discovery Accelerator Supplements NSERC grant to Les Buck.
Prolactin and Extracellular Osmolality Regulate Branchial clc2c Expression in Tilapia
Authors: Keith Paige L.K. , Hunt Bethany L. , Inokuchi Mayu , Yamaguchi Yoko , Seale Andre P. , Lerner Darren T. , Grau E. Gordon , Breves Jason P. 
Published: November 2023

Varying and contending models have been proposed to explain how teleost ionocytes facilitate ion uptake from freshwater environments. A recently characterized member of the clc Cl− channel family (clc2c) has been proposed as a conduit for basolateral Cl− transport by Na+/Cl− cotransporter (ncc)‐expressing ionocytes of stenohaline zebrafish. It is unknown to what extent clc2c is expressed in gill of euryhaline species, such as Mozambique tilapia, and whether expression is modulated in response to extrinsic (salinity) and intrinsic (hormones) factors. Here, we investigated prolactin (Prl) and local osmotic control of clc2c mRNA levels. First, branchial clc2c expression was markedly enhanced in freshwater‐acclimated tilapia compared with seawater‐acclimated tilapia. To investigate endocrine control of this salinity‐dependent expression, we injected hypophysectomized tilapia with ovine Prl. Ovine Prl induced a >8000‐fold increase in clc2c expression from saline‐injected controls. To then test whether Prl regulates clc2c expression in a gill‐autonomous fashion, we incubated gill filaments for 24 hours in the presence of homologous Prls, Prl177 and Prl188. By 24 hours, Prl188 stimulated clc2c expression ~5‐fold from controls. We then incubated filaments in media ranging from 280 to 450 mOsm/kg for 3 hours to investigate the possibility that extracellular osmolality exerts a local effect on clc2c expression. clc2c showed higher expression with decreasing media osmolalities. Collectively, our results suggest that both hormonal and extracellular osmotic conditions direct clc2c expression in branchial ionocytes. We propose that multifactorial modulation of clc2c expression contributes to the excellent adaptability of Mozambique tilapia to variations in environmental salinity.Support or Funding InformationSupported by Start‐Up Funds (Skidmore College) to J.P.B.
Acute Effect of Ischemic Preconditioning on V̇O2max and V̇O2 Kinetics at Supramaximal Intensity in High‐Level Runners: A Randomized Placebo‐ and Nocebo‐Controlled Study
Authors: de Castro Sabino‐Carvalho Jeann Lúccas , Lopes Thiago Ribeiro , Obeid‐Freitas Tiago , Ferreira Thiago Henrique Nunes , Succi Jose Ernesto , Silva Antonio Carlos , Silva Bruno Moreira 
Published: November 2023

BackgroundIschemic preconditioning (IPC; brief cycles of ischemia) has been reported to acutely improve aerobic capacity and performance in recreational athletes. However, placebo and nocebo effects have not been adequately controlled, strict criteria to confirm the maximal oxygen uptake (V̇O2max) have not been used and high‐level aerobic athletes have not been assessed. Therefore, we controlled placebo and nocebo effects to investigate if IPC improves aerobic capacity and performance in high‐level runners.MethodsFifteen men (age = 22 ± 3 years; V̇O2max = 67.7 ± 4.9 mL/kg/min; mean ± SD) and four women (age = 24 ± 4 years; V̇O2max = 55.8 ± 4.1 mL/kg/min) were assessed. All have been training in running teams (5 ± 2 years) and participating in official competitive events. Three interventions were used, in random order [IPC; placebo ultrasound (PL); and resting control (CT)]. A standardized explanation was provided, before interventions were applied, to inform that both IPC and PL would improve performance compared to CT and that IPC and PL would not cause any harm. After each intervention, a maximal incremental test (MIT) was conducted to measure the V̇O2max. Ten minutes later, a supramaximal (peak velocity + 0.5 km/h) constant test was done until voluntary exhaustion. This test was used to verify the V̇O2max, measure the time sustained at V̇O2max and assess aerobic performance [time to exhaustion (TLim)]. Verbal incentive was given by a blinded investigator. Interventions were compared by repeated measures ANOVA, followed by Bonferroni's post hoc, when necessary.ResultsV̇O2max (65.5 ± 6.6, 65.4 ± 7.2, and 64.8 ± 5.8 mL/kg/min for IPC, PL, and CT, respectively; P = 0.52), time at V̇O2max(49 ± 35, 54 ± 45, and 37 ± 24 s; P = 0.36), and V̇O2 kinetics (tau: 29 ± 4, 30 ± 4, and 28 ± 4 s; P = 0.84) were similar among interventions. TLim was longer in IPC (166 ± 13 s) and PL (165 ± 13 s) than CT (143 ± 13 s, P < 0.05). However, TLim was similar between IPC and PL (P > 0.05).ConclusionsIPC improved aerobic performance compared to CT in high‐level runners, but the improvement was not superior to PL. Moreover, V̇O2max, evaluated by strict criteria, time at V̇O2max, and V̇O2 kinetics at supramaximal intensity were unchanged by IPC.Support or Funding InformationJ.L.C.S. and T.O. have been supported by scholarships from FAPESP (2014/15877‐8 and 2015/03572‐0, respectively). The project was funded by FAPESP (2014/25683‐6) and CNPq (461516/2014‐4).
Is There A Relationship Between Pulmonary Capillary Blood Volume And Intrapulmonary Arteriovenous Anastomosis Recruitment During Exercise?
Authors: Tedjasaputra Vincent , Collins Sophie É , Bryan Tracey L , van Diepen Sean , Bouwsema Melissa M , Stickland Michael K 
Published: November 2023

Exercise results in the recruitment of anatomical intrapulmonary arteriovenous anastomoses (IPAVA). There is speculation that IPAVA recruitment may act as a ‘pop‐off’ valve once pulmonary capillaries are fully recruited during exercise to protect the lung from large increases in pulmonary arterial pressure. Recognizing that the pulmonary capillaries are fully recruited in the supine position, we hypothesized that IPAVA recruitment during incremental exercise would initially occur at a pulmonary capillary blood volume (Vc) that approximated the value observed in the supine position. Twenty healthy subjects (9 males, 11 females, means±SD, age: 27±7 yrs, VO2max: 49.9±10.5 mL·kg−1·min−1) performed cycling exercise at 30, 50, 70 and 90% of VO2max. Capillary blood volume (Vc) was determined using the multiple FIO2‐DLCO breath‐hold method in the supine and upright positions at rest, as well as during upright exercise. IPAVA recruitment was evaluated by agitated saline contrast echocardiography. Mean Vc was 80.2±17.2 mL in the resting upright position, which increased to 94.6±24.6 mL when supine (p=0.043). During incremental upright exercise, Vc increased up to 132.9±26.3 mL at peak exercise (p<0.01). IPAVA recruitment was detected in all subjects during exercise, and first occurred at a mean Vc of 93.8±16.0 mL, which is significantly greater than resting upright Vc (p<0.05), but similar to resting supine Vc (p=0.97). Results were similar in men compared to women, and results were consistent when adjusting for alveolar volume. IPAVA recruitment was observed at a capillary blood volume similar to the value observed in the supine position. As the supine position is widely believed to result in the perfusion of all pulmonary capillaries, these data support the hypothesis that recruitment of IPAVAs follows full recruitment of the pulmonary capillaries.Support or Funding InformationProject funding provided by the Natural Sciences and Engineering Research Council (NSERC, PI M. Stickland), and the Canadian Respiratory Research Network (CRRN, PI M. Stickland). V. Tedjasaputra is supported by the The Lung Association of Alberta and NWT graduate studentship. M. Bouwsema was supported by NSERC and Alberta Innovates Health Solutions summer studentships.
Elevated inspired and end‐tidal PCO2 on the International Space Station
Authors: Hughson Richard L , Yee Nicholas , Greaves Danielle 
Published: November 2023

The vision impairment intracranial pressure syndrome (VIIP) has recently been identified in astronauts living in space for long durations on the International Space Station (ISS). Although changes in hydrostatic pressure gradient resulting in chronic increases in cerebral artery and intracranial pressure are regarded as the most likely causes of VIIP, the elevated PCO2 in the atmosphere of the ISS is considered a potential contributor due to the vasodilatory effect of CO2 on cerebral and retinal arterioles. To date, there are no data published on the impact of elevated inspired PCO2 on arterial PCO2 during spaceflight. In the BP Reg study, we measured cardiac output by rebreathing providing an opportunity to obtain several breaths prior to rebreathing in which we could monitor inspired and expired PCO2. Here we report the averages from pre‐rebreathing PCO2 from inspiration and end‐tidal values (as indicators of the arterial PCO2) from 9 male astronauts during maneuvers in pre‐flight upright seated baseline testing and during spaceflight approximately 3 weeks before return to Earth. For each individual, all suitable breaths were averaged to a single value. Inspired PCO2 increased from pre‐flight baseline (0.6±0.12 mmHg) to inflight (3.8±0.44 mmHg, P<0.001). Expired, end‐tidal, PCO2 also increased from pre‐flight baseline (36.0±3.22 mmHg) to inflight (42.1±3.70 mmHg, P=0.004). The difference between end‐tidal PCO2 comparing inflight to pre‐flight (6.1±1.62 mmHg) was greater than the difference between inspired PCO2 comparing pre‐flight to inflight (3.3±0.46 mmHg, P<0.001). These data show that inspired PCO2 is elevated during spaceflight, but rather than an anticipated increase in alveolar ventilation to compensate for this increase in inspired PCO2, there might have been a reduction in alveolar ventilation resulting in an increase in end‐tidal PCO2 which is an indicator of arterial PCO2, although changes in ventilation‐perfusion should be considered. On Earth, a 6 mmHg increase in arterial PCO2 would be expected to increase brain blood flow over 15%; but, in spaceflight there appears to be no increase (Arbeille, 2001). Therefore, further studies are required to examine arterial PCO2 rather than end‐tidal, cerebrovascular reactivity to CO2 and cerebral blood flow to determine if elevated inspired PCO2 might contribute to the incidence of VIIP in astronauts.Support or Funding InformationSupported by Canadian Space Agency
The Role of Prolonged Adenosine Triphosphate Infusion on Rapid Onset Vasodilation
Authors: Dillon Gabrielle , Shepherd John‐Roger , Dinenno Frank , Curry Timothy , Joyner Michael , Ranadive Sushant 
Published: November 2023

Exercise‐induced rapid onset vasodilation produces a temporary rise in skeletal muscle blood flow in humans. The underlying mechanisms for this rapid hyperemia and regulation of muscle blood flow with single contraction are still not well understood. We tested the hypothesis that during a prolonged high dose intrarterial infusion of adenosine triphosphate (ATP; 20 μgrams ·100 mL forearm vol−1·min−1), the rapid onset vasodilatory response post‐single exercise contraction would be reduced compared to that of adenosine (ADO; 23 μgrams ·100 mL forearm vol−1·min−1). 14 healthy young participants (30 ± 1 years) performed a forearm single contraction exercise (20% of maximum) at minute 75 of either ATP (N=8) or ADO (N=6) continuous infusion. Artery diameter and blood velocity were measured using Doppler ultrasound. Forearm vascular conductance (FVC; ml·min−1·100 mmHg−1), time to peak, and area under curve were calculated. The mean resting FVC was higher during ATP (307.15 ± 50.56) and ADO (353.23 ± 43.98) infusion compared to saline infusion (45.17 ± 5.61 and 47.14 ± 5.57) (p<0.05). Compared to ADO, ATP infusion had a lower delta FVC from post‐ to pre‐contraction (174.06 ± 30.75 vs. 276.53 ± 24.90, p<0.05). Area under the curve and time of peak FVC did not significantly differ between drugs. These results suggest a prolonged ATP infusion may have blunted the rapid vasodilatory response more‐so than ADO. Thus, our findings indicate that ATP may be necessary but not obligatory in the rapid onset vasodilation response post‐single muscle contraction in humans.Support or Funding InformationSupported by National Institutes of Health Research Grants HL‐119337 (to M.J. Joyner and F.A. Dinenno) and by CTSA UL1 TR000135. The Caywood Professorship (M.J. Joyner) via the Mayo Foundation also supported this research.
Cutaneous Blood Flow during Intradermal Exogenous Nitric Oxide Administration in Young and Older Adults: Roles for Cyclooxygenase and Calcium‐Activated Potassium Channels?
Authors: Fujii Naoto , Singh Maya Sarah , Minson Christopher T , Brunt Vienna E , Boulay Pierre , Sigal Ronald J , Kenny Glen P 
Published: November 2023

Nitric oxide (NO) increases cutaneous blood flow. We hypothesized that cutaneous blood flow during intradermal administration of sodium nitroprusside (SNP, a NO donor) is in part regulated by cyclooxygenase (COX) and calcium‐activated potassium (KCa) channels in young adults. We also hypothesized that these contributions are diminished in older adults as ageing can reduce COX‐derived vasodilator prostanoids and downregulate KCa channels. In 10 young (3 males and 7 females, 23 ± 5 years) and 10 older (3 males and 7 females, 54 ± 4 years) adults, cutaneous vascular conductance (CVC) was measured at four intradermal forearm skin sites receiving 1) Ringers (Control), 2) 50 mM tetraethylammonium (TEA), a non‐specific KCa channel blocker, 3) 10 mM ketorolac, a non‐specific COX inhibitor, or 4) 50 mM TEA + 10 mM ketorolac. All skin sites were co‐infused with incremental doses of SNP (0.005, 0.05, 0.5, 5, 50 mM each for 25 min). Compared to the Control site, CVC during SNP administration was similar at the ketorolac site (0.005–50mM, all P > 0.05) but was lower at the TEA and TEA + ketorolac sites (0.005–5mM, all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to the Control site during SNP administration (0.005–0.5mM, all P < 0.05), but this increase disappeared when TEA was co‐administered (all P > 0.05). TEA alone did not modulate CVC during SNP administration in older adults (0.005–50mM, all P > 0.05). We show that during intradermal exogenous NO administration, KCa channels, but not COX, contribute to cutaneous blood flow regulation in young adults, while COX reduces cutaneous blood flow by attenuating KCa channel‐dependent cutaneous vasodilation in older adults.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014), and by Canada Foundation for Innovation (Leaders Opportunity Fund, 22529) (funds held by Dr. Glen P. Kenny).
Orthotopic versus Ectopic Tumor Perfusion During Exercise: Implications for Host Tissue Vasoreactivity
Authors: Garcia Emmanuel , Becker Veronika , Gittemeier Elizabeth Marie , Opoku‐Acheampong Alexander Boadu , McCullough Danielle , Behnke Bradley Jon 
Published: November 2023

The microenvironment of solid tumors, like those present in prostate cancer, demonstrate heterogeneous blood flow patterns and regions of hypoxia that can impact the efficacy of radiation therapy. Studies designed to evaluate tumor hypoxia have utilized both ectopic (e.g. tumor cells implanted subcutaneously) and orthotopic (i.e. tissue of origin) tumor models. In orthotopic models, exercise has been demonstrated to reduce tumor hypoxia, whereas in ectopic models the effects of exercise are equivocal. Preliminary studies from our laboratory found a significant increase in blood flow to orthotopic prostate tumors (increase of 209 ± 22% vs. resting) versus a reduction in blood flow in ectopic tumors (decrease of 25 ±5 % vs. resting) during moderate intensity exercise (50–60% of maximal aerobic capacity)). Given this data, it was hypothesized that subcutaneous adipose arterioles and skin arterioles (ectopic host tissue) would have greater vasoconstriction versus prostate arterioles (orthotopic host tissue) in response to the alpha‐adrenergic agonist norepinephrine (NE). Six‐month old male Copenhagen rats (n=20) were used in this study. Resistance arterioles (<150 μm diameter) from the ventral lobe of the prostate, the rear flank skin, and the immediate subcutaneous adipose tissue were isolated and cannulated for in vitro analysis of vasomotor function. The latter two tissues form the bulk of the tissue representing the site of typical ectopic tumor models. The vessels were allowed to develop spontaneous tone. Thereafter, vasoconstriction to cumulative doses of NE (10−9 – 10−4 M) were recorded. There was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%; P<0.05) versus both skin (59 ± 8%) and prostate (55 ± 7%) arterioles. There were no significant differences in vasoconstriction between skin and prostate arterioles. In conclusion, during exercise when sympathetic nerve activity is increasing, the greater vasoconstriction in the host‐tissue arterioles of ectopic versus orthotopic tumor models likely contribute to the diametrically opposing rest‐to‐exercise tumor blood flow responses. Therefore, these data are critical to consider when selecting appropriate tumor models for exercise study designs.Support or Funding InformationAmerican Cancer Society (RSG‐14‐150‐01‐CCE), American Physiological Society and the National Institutes of Health (NHLBI; 1 R25 HL115473‐01).
Extracellular matrix affects endothelial cell attachment under shear flow
Authors: Chiu Yi‐Fan , Huang Bin 
Published: November 2023

Shear flow plays an important role in cardioprotection. In the present In vitro study, shear flow is processed on a glass slide that coated with biomatrix so that the endothelial cells (ECs) can grow on it and then exposed to the shear flow. However, the detachment of ECs always hinders scientists to study the molecular aspect of cardioprotective mechanism. In the present study, the glass slides were washed either by hydrochloride (acidic wash) or sodium hydroxide (basic wash). After sterilized by ethanol, the glass slides were coated with three matrixes, poly‐L‐Lysine, fibronectin and collagen separately. Exposed the ECs to the shear flow of 5 dynes/cm2 and 20 dynes/cm2 for 2 hours, we investigated the attached cell number and their viability. The results showed that basic wash coupled with the coating of fibronectin has the best binding efficiency as compared to the others. The sustained expression of focal adhesion kinase (FAK) also supports our observation. As a result, our study provides a considerable application for the research of shear flow.Support or Funding InformationMOST 104‐2632‐M‐037‐001, KMU‐TP104E13, KMU‐O104003, KMU‐O105001
Microvascular Responsiveness to Exogenous H2S is similar between Normotensive and Hypertensive Adults
Authors: Kutz Jessica L , Greaney Jody L , Santhanam Laskshmi , Alexander Lacy M 
Published: November 2023

Hydrogen sulfide (H2S) is an endothelium‐derived hyperpolarizing factor (EDHF) that elicits cutaneous vasodilation in healthy young adults. H2S also functionally interacts with both nitric oxide (NO) and cyclooxygenase (COX) signaling pathways. Despite noted vascular dysfunction in hypertensive animal models, vascular responsiveness to exogenous H2S is preserved. The aim of this study was to (1) examine cutaneous vascular responsiveness to exogenous H2S in normotensive (NTN) and hypertensive (HTN) adults and (2) to assess the functional interaction of H2S with the NO and COX vasodilatory signaling pathways. We hypothesized that vascular responsiveness to exogenous H2S would be preserved but that functional interactions with both NO and COX would be diminished in HTN adults. Skin blood flow (laser Doppler flowmetry) responses were measured during graded intradermal microdialysis infusion of the H2S donor Na2S alone (CONTROL; 0.01mM – 100mM) and during co‐infusion with the non‐specific NO synthase inhibitor L‐NG‐Nitroarginine Methyl Ester (L‐NAME; 20 mM), the non‐selective COX inhibitor ketorolac (KETO; 10 mM), and combined L‐NAME+KETO in the ventral forearm of 7 NTN [age: 56±1 yrs; resting blood pressure (BP) 110±4/73±2 mmHg) and 7 HTN (age: 60±3 yrs; resting BP 144±5/86±3 mmHg) adults. Sigmoidal dose‐response curves were generated and the logEC50 was used as an index of vascular responsiveness. Cutaneous vascular responsiveness to Na2S was not different between groups (1.37±0.12 NTN v. 1.57±0.13 HTN; P>0.05). In NTN adults, there was a rightward shift in the dose‐response curve during L‐NAME (1.83 ± 0.07), KETO (2.07 ± 0.18), and COMBO infusion (2.33 ± 0.13; P<0.05 for all). In contrast, in HTN adults, separate infusion of L‐NAME (1.64 ± 0.06) or KETO (2.05 ± 0.20) had no effect (P>0.05 for both) on Na2S‐induced vasodilation; however, combined inhibition elicited a rightward shift in the dose‐response curve (2.25 ± 0.20; P<0.01). These data suggest that vascular end‐organ responsiveness to exogenous H2S is preserved in HTN adults, despite noted reductions in the contribution of the NO and COX signaling pathways to Na2S‐induced vasodilation.Support or Funding InformationNIH HL093238‐06