bluuebunny/crossref_metadata_2025_split huggingface dataset:
The inhibition of NOS down regulates adenosine production in the interstitial space of rat skeletal muscle
Authors: Zhao Yi , Smith Ashley A , Fabris Sergio , MacLean David A 
Published: June 2021

It is generally accepted that vasodilatation in skeletal muscle is regulated in part by both adenosine (Ado) and nitric oxide (NO). It has previously been shown by our laboratory that perfusion of 60 μM of ATP into the interstitial space (via microdialysis) more than doubled the interstitial Ado concentration (0.15±0.02 to 0.33±0.04 μM), mediated predominantly by the 5′‐ectonucleotidase. However, a thorough examination of the relationship between NO and Ado production in the interstitial space has yet to be examined. Anesthetized Sprague Dawley rats had microdialysis fibers inserted into the gastrocnemius muscle of each leg and perfused with saline (baseline control) and then with either 10 mM L‐NAME (NOS inhibitor, n = 8 rats, n = 31 probes) or 10 mM L‐NAME + 60 μM ATP (n = 6 rats, n = 14 probes) for 20 minutes at a rate of 5 μl/min. Interestingly, during L‐NAME perfusion interstitial Ado levels were decreased (P<0.05) from baseline levels (0.20±0.01 μM) to below HPLC detection limits. The addition of ATP to the perfusate in an effort to promote Ado production via the 5′‐ectonucleotidase did not restore interstitial Ado concentrations. These data clearly show that the inhibition of NOS dramatically attenuates Ado production, which cannot be reversed by the addition of ATP. These finding strongly suggest that skeletal muscle interstitial Ado production is regulated by NO and/or NOS activity.Supported by NSERC
K2P‐like current in freshly dissociated mouse thoracic aorta: the impact on thoracic aorta diameter
Authors: Bychkov Rostislav , Hayoz Sandébastien , Soliman Youssef , Cubano Luis , Maldonado Hector 
Published: June 2021

BackgroundIt was suggested that K+ channels family identified as "two‐pore potassium channels (K2P)" function as leak K+ efflux that regulates membrane potential complementary to Ca2+, ATP and voltage dependent K+ channels. Does opening of K2P channels dilate vascular beds, or do they tune membrane potential only?Methods and resultsPatch‐clamp technique was used to record an ATP‐γs elicited delayed K+‐current in freshly dissociated myocytes. This current was not inhibited by a "cocktail" of K+ channels blockers (TEA, 4AP, charibdotoxin, apamin, glibenclamide). Tested purinergic agonists (ATP, UTP) – except for ADP ‐ activated delayed K+‐current indicating that at least P2Y11 receptor stimulates delayed K+‐current. 12,13‐didecanoate also stimulated this current. ATPγs‐elicited K+‐current amplitude decreased in staurosporine and G6850 pretreated cells. Acid pH (7 and 6) inhibited when basic pH (8) stimulated amplitude of ATPγs‐elicited K+‐current. ATP‐γs produced a vasodilation in endothelium‐denuded thoracic aorta rings contracted by the K+‐channels blockers and pre‐treated by carbenoxolone. Vasodilation was inhibited by acid pH (6).ConclusionsOur results demonstrate that ATP‐γs dilates pre‐stretched thoracic aorta rings via stimulation of pH sensitive K+‐current through P2Y receptors. Taken together our data provide new cellular mechanism of vasoregulation via K2P‐like channels.
The small GTPase RhoA Stimulates the Contraction of Airway Smooth Muscle (ASM) by Regulating Actin Polymerization rather than Myosin Light Chain (MLC) Phosphorylation
Authors: Zhang Wenwu , Gunst Susan J 
Published: June 2021

Activation of RhoA has been shown to inhibit MLC phosphatase activity, thus increasing MLC phosphorylation and force in some smooth muscle. In ASM, actin polymerization is required for active contraction in addition to MLC phosphorylation. RhoA can regulate cytoskeletal processes and actin polymerization. We evaluated whether RhoA regulated the contraction of ASM primarily through its effects on MLC phosphorylation or actin polymerization. RhoA activity was inhibited in canine tracheal smooth muscle tissues by expressing the inactive RhoA mutant, RhoA T19N, or by treating tissues with the cell permeant RhoA inhibitor, C3 exoenzyme. RhoA inactivation inhibited ACh‐induced contractile force by 60–70%, inhibited ACh‐induced actin polymerization, and also caused a small (10–20%) decrease in MLC phosphorylation. Tissues were treated with the phosphatase inhibitor, calyculin A, by inactivate MLC phosphatase. Calyculin A induced MLC phosphorylation and contraction in the absence of ACh and potentiated MLC phosphorylation induced by ACh, but it did not affect ACh stimulated contraction or actin polymerization. However, inhibition of MLC phosphatase by calyculin A did not prevent the depression of force caused by the RhoA inactivation. This suggests RhoA activation regulates ASM contraction primarily through its effects on actin dynamics.Supported by HL29289, HL074099, ALA, and NIH T32 Grant GM12453‐03
Post‐exercise feeding attenuates proteolytic gene expression in human skeletal muscle
Authors: Harber Matthew , Konopka Adam , Jemiolo Bozena , Trappe Todd , Trappe Scott , Reidy Paul 
Published: June 2021

The purpose of this investigation was to assess the influence of feeding after a single session of aerobic exercise on the expression of genes involved in skeletal muscle remodeling. Eight recreationally active males (25±1y; VO2max: 52±2 ml·kg−1·min−1) performed 60‐min of cycle ergometry at 72±1% intensity on two occasions in a counter‐balanced design. Trials differed only in the post‐exercise nutritional intervention. Subjects ingested a non‐caloric placebo (FAST) beverage or a beverage containing (per kg body weight): 5kcal, 0.83g carbohydrate, 0.37g protein and 0.28g fat (FED) immediately and 1h after exercise. Muscle biopsies were obtained at 2 and 6h post‐exercise for the assessment of mRNA expression. Feeding attenuated (P<0.05) the mRNA expression of proteolytic factors MuRF‐1 (6h) and calpain‐2 (2 and 6h) post‐exercise but did not alter FOXO3A, calpain‐1, CASPASE3, or myostatin mRNA expression compared to FAST. Myogenic regulatory factor (MRF4) mRNA was also attenuated (P<0.05) at 2 and 6h post‐exercise in FED compared to FAST. The mRNA expression of mitochondrial factors PGC‐1α and TFAM were not influenced by feeding in the post‐exercise state. These data indicate that post‐exercise nutrient intake attenuates the expression of factors involved in the ubiquitin‐proteosome and Ca++ dependent protein degradation pathways.Supported by a grant from the Gatorade Sports Science Institute
Enhanced transforming growth factor β (TGF‐β) signaling and fibrogenesis in fetal skeletal muscle of obese sheep at late gestation
Authors: Huang Yan , Yan Xu , Zhu Mei J , Ford Stephen P , Nathanielsz Peter W , Du Min 
Published: June 2021

INTRODUCTIONMaternal obesity is increasing at an alarming rate. The objective of this studywas to evaluate the effect of maternal obesity on fibrogenesis in fetal skeletal muscle in late gestation when ovine fetal muscle matures.METHODSNon‐pregnantewes were assigned to a control (Con, fed 100% of NRCnutrient recommendations, n = 6) or obesogenic (OB, fed150% of NRC recommendations, n = 6) diet from 60 days before to 135 days after conception (gestation =148 days) when the fetal semitendenosus (St) muscle wassampled for trichrome staining, immunoblotting and real‐time quantitative PCR analyses.RESULTSThe total area of collagen in the cross‐sections of St muscle increased by 105.1 ± 5.9% (P = 0.05) in fetuses of OB compared with Con mothers. The expression of precursor TGF‐β in OB fetal muscle was 177.3 ± 47.6% higher (P < 0.05) than Con fetal muscle, indicating activation of TGF‐β signaling. p38 promotes TGF‐β signaling; the concentration of phospho‐p38 was 74.7 ± 23.6% higher (P < 0.05) in OB fetal muscle, as well as the ratio of phospho‐p38/total p38 (83.2 ± 20.4%, P < 0.05). The mRNA expression of Smad7 and fibronectin is regulated by TGF‐β signaling. An increase of 327.9 ± 168.0% (P < 0.05) and 188.9 ± 82.1% (P < 0.05) respectively was observed for the mRNA expression of Smad7 and fibronectin in OB fetal muscle compared with Con.CONCLUSIONSThese data demonstrate that maternal obesity enhanced fibrogenesis in fetal muscle in late gestation associated with up‐regulation of the TGF‐β/p38 signaling pathway. These changes are expected to negatively affect the properties of offspring skeletal muscle. (Supported by NIH 1R03HD057506 and Wyoming INBRE P20RR016474)
Soleus muscle of Down syndrome (DS) mice exhibits elevated markers of oxidative and nitrosative stress
Authors: Cowley Patrick M , DeRuisseau Keith C 
Published: June 2021

Individuals with DS have a reduced capacity for voluntary force generation compared to individuals with and without other forms of intellectual disability. Oxidative stress (OS) is thought to be a key factor in DS pathologies that may be the result of triplication and over‐expression of copper‐zinc superoxide dismutase (CuZnSod). Our aim was to assess markers of OS and nitrosative stress (NS) in soleus muscle of a well established mouse model of DS, the Ts65Dn mouse, which is segmental trisomic for CuZnSod. We hypothesized that soleus muscle of Ts65Dn mice would exhibit elevated markers of OS and NS compared to soleus from wild‐type (WT) controls. Eighteen (n=9 per group) 4–7 month old male Ts65Dn and WT mice were used in these experiments. Western blot analysis was performed to quantify the relative expression of markers of OS (4‐hydroxy‐nonenal (4‐HNE)) and NS (3‐nitrotryosine (3‐NT)). Levels of soleus muscle 4‐HNE and 3‐NT were 476% and 276% higher in Ts65Dn mice (p<0.05), respectively. These findings suggest that soleus muscle from Ts65Dn mice exhibits elevated markers of OS and NS, which is consistent with the human phenotype of DS. Additionally, preliminary microarray analysis identified 43 up‐regulated and 66 down‐regulated genes in soleus of Ts65Dn compared to WT mice (p<0.001, ± 1.5‐fold). We are currently categorizing these differentially expressed genes.Supported by Syracuse University SOE
Hydration effects on vascular fluid dynamics during acute exposure to 3,048 m
Authors: Castellani John William , Muza Stephen R , Kenefick Robert W , Sawka Michael N 
Published: June 2021

Vascular fluid dynamics [plasma volume (PV) and total circulating protein (TCP)] during acute (8‐h) high‐altitude (ALT) exposure are poorly described and the impact of hypohydration (HYPO) on these responses has not been reported. Seven men (25 ± 7 yr; 44.1 ± 4.9 ml/kg/min V02peak completed 4 experimental trials in a counterbalanced design. Subjects were sea level (SL) residents who had completed 4 days of heat acclimation prior to the trials. Trials were: a) SL‐Euhydrated (SL‐EUH); b) SL‐HYPO; c) ALT‐EUH; and d) ALT‐HYPO. The day before each trial, subjects completed a standardized exercise‐heat stress bout either with (EUH) or without (HYPO, −4% body mass) fluid replacement. Subjects maintained hydration status overnight and the following morning entered a hypobaric chamber (27°C) and rapidly ascended to either 150 m or 3,048 m (O2 saturation = 89 ± 3 %). During each 8 h trial, subjects were sedentary except for completing a standardized submaximal exercise bout (60 min) between 1–2.5 h of exposure. Plasma osmolality was not altered by ALT but was increased (291 ± 5 to 300 ± 6 mosmol/kg) by HYPO. PV was not altered by ALT (3.37 ± 320 L) but was reduced (320 ± 120 ml, 9.5%, p<0.01) by HYPO. TCP (268 ± 30 g) was not altered by ALT or HYPO. These data indicate that vascular fluid dynamics are not altered during the initial 8h of exposure to 3,048 m regardless of hydration status.Not reflecting official views of the Army or DoD.
Peripheral chemoreflex sensitivity and sympathetic nerve activity are normal in breath hold divers during training season
Authors: Breskovic Toni , Ivancev Vladimir , Banic Ivana , Jordan Jens , Dujic Zeljko 
Published: June 2021

Breath hold divers are exposed to repeated massive arterial oxygen desaturation, which could perturb chemoreflexes. Therefore, we tested the hypothesis that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is present during the training season. We determined ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 10 breath hold divers and 11 matched control subjects at the end of the season of intense apnea trainings. Baseline MSNA frequency was 30±4 bursts/min in control subjects and 25±4 bursts/min in breath hold divers (P=0.053). During hypoxia burst frequency and total sympathetic activity increased similarly in both groups. Sympathetic activity normalized during 30 minute recovery period. Hypoxia‐induced stimulation of minute ventilation was similar in both groups. Hypoxia increased heart rate and cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. We conclude that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is paradoxically preserved in apnea divers during the training season.This study was supported by the Croatian Ministry of Science, Education and Sports.
Monocyte Chemoattractant Protein‐1(MCP‐1) released from hypoxic alveolar macrophages activates systemic mast cells
Authors: Donham Paula , Chao Jie , Viets Zachary , Wood John G , Gonzalez Norberto C 
Published: June 2021

Alveolar hypoxia (FIO2 = 0.1) produces a rapid and widespread systemic inflammation in rats. We have shown that the inflammation is not initiated by low tissue PO2 but by a circulating mediator(s) released from alveolar macrophages (AMØ). This substance(s) activates mast cells (MC) which, in turn, initiate the inflammation. The MC secretagogue MCP‐1 is released by primary cultures of hypoxic AMØ, suggesting a role in this process. If MCP‐1 mediates the inflammation: 1) substances that prevent AMØ activation by hypoxia would also prevent MCP‐1 release, and 2) MC immersed in hypoxic AMØ supernatant would show MCP‐1 –dependent degranulation.Primary cultures of rat AMØ exposed to hypoxia (10, 5 and 0 % O2) showed a respiratory burst evidenced as a release of H2O2; this was accompanied by a release of MCP‐1 into the supernatant; 2) both the respiratory burst and the release of MCP‐1 were blocked by pretreatment of rats with dexamethasone; 3) normoxic MC immersed in supernatant of hypoxic AMØ underwent degranulation; 4) MC degranulation was blocked by pretreatment of MC with MCP‐1 receptor blocker.ConclusionsThe results show that AMØ activated by hypoxia release MCP‐1 which, in turn, produces MC degranulation. These data support a role for MCP‐1 in the initiation of the systemic inflammation of alveolar hypoxia in intact animals.Supported by NIH 39443‐18, AHA 0815652G and APS Frontiers in Biology
Evidence that hypoxia‐induced pulmonary vasoconstriction in humans is primarily a post‐capillary event
Authors: Taylor Bryan Joseph , Snyder Eric , Olson Thomas , O'Malley Kathy , Johnson Bruce 
Published: June 2021

BackgroundExposure to hypoxia causes pulmonary vasoconstriction (HPV) and may contribute to the pathogenesis of HAPE. The site of HPV, however, is controversial. While the majority of data suggests HPV occurs in the pulmonary arterioles (precapillary), there is evidence that HPV may also occur in postcapillary vessels. Expansion of pulmonary capillary blood volume (Vc) is primarily passive and thus closely linked to cardiac output (Q).PurposeTo examine relationships between Q and Vc during exposure to hypoxia and fluid loading.Methods/ResultsHealthy adults (n=25, age=31±2 yr) reported to the lab for 2 exposures: 1) 17‐h 12.5% FIO2 in a hypoxia tent, and 2) fluid loading using IV saline (30 ml/kg over ~15 min). Q, Vc and Dm (alveolar‐capillary conductance) were measured using a rebreathe method with small amounts of C2H2, CO and NO gas. Saline infusion caused an increase in Q (32±6%, P<0.01) and Vc (39±13%, P<0.05), and a decrease in Dm (−9±3%, P<0.05). Vc/Q was not different pre‐ vs post‐saline (17±2 vs 18±3, P=0.40). Hypoxic exposure caused an increase in pulmonary arterial pressure (67±11%, P<0.01), Vc (57±20%, P=0.04) and Dm (35±6%, P<0.01) despite no change in Q (0.2±2.8%, P=0.98). Vc/Q was greater post‐ vs. pre‐hypoxia (24±4 vs. 17±2, P=0.06).ConclusionThe rise in Vc with a constant Q during hypoxic exposure suggests a post capillary site for HPV causing the expansion of the pulmonary capillary bed. HL71478.
Ventilatory Changes After Active Heat Acclimation for Multiday Ultramarathon Races in the Sahara Desert
Authors: Serna Selima D , Clegg Miriam E , White Matthew D 
Published: June 2021

To determine the effect of active heat acclimation (HA) on ventilatory responses, 4 endurance‐trained athletes (42.0 ± 5.7 y, mean ± SD) underwent 10 day of activity in 35–40°C and ~15% RH conditions to prepare for multiday ultramarathon races in the Sahara desert. Exercise during HA included 1 h/day of running at ≥50% maximal oxygen consumption (VO2max). Physiological assessments included pre‐ and post‐HA VO2max, heart rate (HR), esophageal (Tes), rectal (Tre), and skin temperatures (4 sites). Pre‐ and post‐HA VO2max values were not significantly different (52.8 ± 4.0 vs 52.0 ± 4.6 mL·kg−1·min−1, p = 0.35). Attainment of HA was confirmed by a significant reduction in exercise HR (p < 0.01) and trends (p=0.12) for reductions in both Thermal Comfort ratings and Borg Ratings of Perceived Exertion over the 10‐d HA period. During incremental exercise, from pre‐ to post‐HA, the ventilatory equivalent for O2 (VE/VO2) increased from 28.6 ± 1.0 to 30.2 ± 1.0 (p = 0.06), whereas the ventilatory equivalent for CO2 (VE/VCO2) showed no change (29.6 ± 0.8 vs 29.8 ± 2.0, p = 0.37). These preliminary data suggest that active HA increases ventilatory responses independently of an exercise training effect.Supported by NSERC, Canadian Foundation for Innovation.
Changes in central venous pressure during heat stress as a possible predictor of compromised blood pressure control during simulated hemorrhage
Authors: Ganio Matthew Stueck , Brothers R. Matthew , Wingo Jonathan E. , Keller David M. , Crandall Craig G. 
Published: June 2021

The extent to which heat stress compromises blood pressure control is quite variable between individuals; some are intolerant to a simulated hemorrhagic challenge while heat stressed, with others being relatively tolerant. The objective of this study was to identify if the magnitude of reduction in central venous pressure (CVP) during heat stress explains the variability in tolerance to a hemorrhagic challenge. Simulated hemorrhage was imposed via lower body negative pressure to pre‐syncope on 20 subjects during passive heating. Tolerance was quantified with a cumulative stress index (CSI), and the 8 subjects with the lowest and the 8 with the highest CSI were categorized as low‐ and high‐tolerant, respectively. The increase in core body temperature was similar between groups (1.45 ± 0.11 versus 1.41 ± 0.09°C, P = 0.44), and by design CSI was greater for the high tolerant group (439 ± 183 vs 86 ± 39 CSI units; P < 0.001). Although heat stress decreased CVP in the low (6.6 ± 2.6 to 0.8 ± 2.1 mmHg) and the high (7.6 ± 2.0 to 2.0 ± 3.0 mmHg) tolerant groups (P < 0.001), the magnitude of this reduction was not different between groups (low: 5.9 ± 1.4; high: 5.6 ± 2.1 mmHg; P=0.53). Contrary to our hypothesis, differences in blood pressure control during simulated hemorrhage are not related to differences in the magnitude of the heat stress‐induced reduction in CVP.Supported by NIH Grants HL61388 & HL84072 & TREi
Acute volume infusion preserves left ventricular end diastolic volume during combined heat and simulated hemorrhage
Authors: Brothers R. Matthew , Wilson Thad , Dalsgaard Morten , Bundgaard‐Nielsen Morten , Pecini Redi , Secher Niels H , Crandall Craig G. 
Published: June 2021

Heat stress compromises blood pressure (BP) control during a simulated hemorrhagic challenge, while acute volume loading attenuates this response. This study tested the hypothesis that the mechanism of preserved BP control during heat stress + volume loading is, in part, through preservation of left ventricular end diastolic volume (LVEDV). LVEDV was measured in nine subjects during normothermia (NT), after an increase in pulmonary artery blood temperature of 1.3 ± 0.2 °C (HS; P < 0.05), and after volume infusion (HS + Inf). In each condition, supine LVEDV was assessed via echocardiography, by the Simpson biplane method, prior to and during simulated hemorrhage, evoked via 30 mmHg lower body negative pressure (LBNP). LVEDV was reduced by HS (NT: 148 ± 26 ml, HS: 126 ± 31 ml; P < 0.05), however, this fall was attenuated by HS + Inf (HS + Inf: 133 ± 25 ml; P > 0.05 relative to NT and HS). During simulated hemorrhage, the reductions in LVEDV were similar between NT (45 ± 20 ml) and HS (52± 20 ml), whereas the reduction in LVEDV after volume infusion (22 ± 22 ml) was attenuated relative to NT and HS (P < 0.05). Importantly, infusion resulted in an LVEDV during LBNP that was significantly elevated (111 ± 26 ml) relative to HS alone (74 ± 25 ml). Improved control of BP following volume infusion during HS occurs in part by attenuating the reduction in LVEDV to a simulated hemorrhagic challenge.Supported by NIH Grant NIH‐HL61388 & HL84072
Integrity of paraventricular nucleus is critical for thermoregulation adjustments during exercise
Authors: Guimarães Juliana Bohnen , Wanner Samuel Penna , Coimbra Cândido Celso 
Published: June 2021

Exercise induced‐hyperthermia results from the imbalance between heat production and dissipation, being capable of interfering on performance. Anatomical and physiological evidences support that the paraventricular nucleus of hypothalamus (PVN) is involved in central pathways modulating the sympathetic activity of thermoregulatory effectors, including the rat's tail vasodilation that is crucial for heat dissipation during exercise. The aim of this study was to verify the participation of PVN on thermoregulatory adjustments during exercise. Male Wistar rats (250–350 g) were submitted to bilateral electrolytic lesion of PVN (n=4) and with control rats were performed sham surgery (n=6). Core body temperature (Tb) and tail skin temperature (Ts) were continuously measured during exercise (18/min, 5% inclination) until fatigue. Ts was taken as an index of vasodilation and heat dissipation. Time to fatigue was 33.4% lower in PVN‐lesioned rats. However, heat storage rate was higher in PVN‐lesioned rats than control (10.4 ± 1.8 cal/min, PVN‐lesioned rats vs. 4.1 ± 0.2 cal/min, control; p<0.05). We also observed a higher threshold for tail vasodilation in PVN‐lesioned rats (0.6 ± 0.0 ° C PVN‐lesioned vs. 0.3 ± .0.0 °C, control; p<0.05). Our results indicate that integrity of PVN interferes with heat balance during exercise by altering heat dissipation.Support: CNPq, FAPEMIG, CAPES.