RESUMEN
High-altitude (HA) hypoxia may alter the structural-functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n = 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex-, age- and body mass index-matched healthy highlanders (n = 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2 ) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2 and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light-chain (NF-L) and T-tau were consistently lower and cognition comparable to lowlanders following chronic-HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia. KEY POINTS: High-altitude (HA) hypoxia has the potential to alter the structural-functional integrity of the neurovascular unit (NVU) in humans. For the first time, we examined to what extent chronic and lifelong hypoxia impacts multimodal biomarkers reflecting NVU structure and function in lowlanders and native Andean highlanders. Despite lowlanders presenting with a reduction in systemic oxidative-nitrosative stress and maintained cerebral bioenergetics and cerebrovascular function during chronic hypoxia, there was evidence for increased axonal injury and cognitive impairment. Compared to lowlanders at sea level, highlanders exhibited elevated vascular NO bioavailability, improved dynamic regulatory capacity and cerebrovascular reactivity, comparable cerebral substrate delivery and neurovascular coupling, and maintained cognition. Unlike lowlanders following chronic HA, highlanders presented with lower concentrations of S100B, neurofilament light chain and total tau. These findings highlight novel integrated adaptations towards the regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.
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Mal de Altura , Humanos , Masculino , Dióxido de Carbono , Altitud , Hipoxia , Aclimatación/fisiología , Oxidación-Reducción , Óxido Nítrico , HomeostasisRESUMEN
NEW FINDINGS: What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic-cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. ABSTRACT: High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80-90% of maximal workload (Wmax ) interspaced by 3-min active rest at 50-60% Wmax . Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39-10.0 Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P < 0.0001 for all), but a time-domain index of aortic-cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P < 0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P < 0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P = 0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P < 0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.
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Presión Arterial , Hemodinámica , Masculino , Humanos , Adulto Joven , Adulto , Hemodinámica/fisiología , Presión Arterial/fisiología , Ejercicio Físico/fisiología , Ultrasonografía Doppler Transcraneal , Volumen Sistólico/fisiología , Presión Sanguínea/fisiologíaRESUMEN
Hypoxia has the potential to impair cognitive function; however, it is still uncertain which cognitive domains are adversely affected. We examined the effects of acute hypoxia (â¼7 h) on central executive (Go/No-Go) and non-executive (memory) tasks and the extent to which impairment was potentially related to regional cerebral blood flow and oxygen delivery (CDO2 ). Twelve male participants performed cognitive tasks following 0, 2, 4 and 6 h of passive exposure to both normoxia and hypoxia (12% O2 ), in a randomized block cross-over single-blinded design. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) blood velocities and corresponding CDO2 were determined using bilateral transcranial Doppler ultrasound. In hypoxia, MCA DO2 was reduced during the Go/No-Go task (P = 0.010 vs. normoxia, main effect), and PCA DO2 was attenuated during memorization (P = 0.005 vs. normoxia) and recall components (P = 0.002 vs. normoxia) in the memory task. The accuracy of the memory task was also impaired in hypoxia (P = 0.049 vs. normoxia). In contrast, hypoxia failed to alter reaction time (P = 0.19 vs. normoxia) or accuracy (P = 0.20 vs. normoxia) during the Go/No-Go task, indicating that selective attention and response inhibition were preserved. Hypoxia did not affect cerebral blood flow or corresponding CDO2 responses to cognitive activity (P > 0.05 vs. normoxia). Collectively, these findings highlight the differential sensitivity of cognitive domains, with memory being selectively vulnerable in hypoxia. NEW FINDINGS: What is the central question of this study? We sought to examine the effects of acute hypoxia on central executive (selective attention and response inhibition) and non-executive (memory) performance and the extent to which impairments are potentially related to reductions in regional cerebral blood flow and oxygen delivery. What is the main finding and its importance? Memory was impaired in acute hypoxia, and this was accompanied by a selective reduction in posterior cerebral artery oxygen delivery. In contrast, selective attention and response inhibition remained well preserved. These findings suggest that memory is selectively vulnerable to hypoxia.
Asunto(s)
Cognición , Hipoxia , Humanos , Masculino , Atención , Circulación Cerebrovascular/fisiología , Cognición/fisiología , Oxígeno , Tiempo de ReacciónRESUMEN
NEW FINDINGS: What is the central question of this study? What are the molecular, cerebrovascular and cognitive biomarkers of retired rugby union players with concussion history? What is the main finding and its importance? Retired rugby players compared with matched controls exhibited lower systemic nitric oxide bioavailability accompanied by lower middle cerebral artery velocity and mild cognitive impairment. Retired rugby players are more susceptible to accelerated cognitive decline. ABSTRACT: Following retirement from sport, the chronic consequences of prior-recurrent contact are evident and retired rugby union players may be especially prone to accelerated cognitive decline. The present study sought to integrate molecular, cerebrovascular and cognitive biomarkers in retired rugby players with concussion history. Twenty retired rugby players aged 64 ± 5 years with three (interquartile range (IQR), 3) concussions incurred over 22 (IQR, 6) years were compared to 21 sex-, age-, cardiorespiratory fitness- and education-matched controls with no prior concussion history. Concussion symptoms and severity were assessed using the Sport Concussion Assessment Tool. Plasma/serum nitric oxide (NO) metabolites (reductive ozone-based chemiluminescence), neuron specific enolase, glial fibrillary acidic protein and neurofilament light-chain (ELISA and single molecule array) were assessed. Middle cerebral artery blood velocity (MCAv, doppler ultrasound) and reactivity to hyper/hypocapnia ( CVR CO 2 hyper ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hyper}}}$ / CVR CO 2 hypo ${\mathrm{CVR}}_{{\mathrm{CO}}_{\mathrm{2}}{\mathrm{hypo}}}$ ) were assessed. Cognition was determined using the Grooved Pegboard Test and Montreal Cognitive Assessment. Players exhibited persistent neurological symptoms of concussion (U = 109(41) , P = 0.007), with increased severity compared to controls (U = 77(41) , P < 0.001). Lower total NO bioactivity (U = 135(41) , P = 0.049) and lower basal MCAv were apparent in players (F2,39 = 9.344, P = 0.004). This was accompanied by mild cognitive impairment (P = 0.020, 95% CI, -3.95 to -0.34), including impaired fine-motor coordination (U = 141(41) , P = 0.021). Retired rugby union players with history of multiple concussions may be characterised by impaired molecular, cerebral haemodynamic and cognitive function compared to non-concussed, non-contact controls.
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Traumatismos en Atletas , Conmoción Encefálica , Disfunción Cognitiva , Fútbol Americano , Humanos , Jubilación , Traumatismos en Atletas/complicaciones , Óxido Nítrico , Rugby , Conmoción Encefálica/complicaciones , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/psicología , Disfunción Cognitiva/complicaciones , BiomarcadoresRESUMEN
Although the ergogenic effects of 3-6 mg/kg caffeine are widely accepted, the efficacy of low doses of caffeine has been discussed. However, it is unclear whether the ergogenic effects of caffeine on jump performance are dose responsive in a wide range of doses. This study aimed to examine the effect of very low (1 mg/kg) to moderate doses of caffeine, including commonly utilized ergogenic doses (i.e., 3 and 6 mg/kg), on vertical jump performance. A total of 32 well-trained collegiate sprinters and jumpers performed countermovement jumps and squat jumps three times each in a double-blind, counterbalanced, randomized, crossover design. Participants ingested a placebo or 1, 3, or 6 mg/kg caffeine 60 min before jumping. Compared with the placebo, 6 mg/kg caffeine significantly enhanced countermovement jump (p < .001) and squat jump (p = .012) heights; furthermore, 1 and 3 mg/kg of caffeine also significantly increased countermovement jump height (1 mg/kg: p = .002, 3 mg/kg: p < .001) but not squat jump height (1 mg/kg: p = .436, 3 mg/kg: p = .054). There were no significant differences among all caffeine doses in both jumps (all p > .05). In conclusion, even at a dose as low as 1 mg/kg, caffeine improved vertical jump performance in a dose-independent manner. This study provides new insight into the applicability and feasibility of 1 mg/kg caffeine as a safe and effective ergogenic strategy for jump performance.
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Rendimiento Atlético , Sustancias para Mejorar el Rendimiento , Humanos , Cafeína/farmacología , Sustancias para Mejorar el Rendimiento/farmacología , Método Doble Ciego , Estudios CruzadosRESUMEN
We examined the acute impact of both low- and high-glycemic index (GI) breakfasts on plasma brain-derived neurotrophic factor (BDNF) and dynamic cerebral autoregulation (dCA) compared with breakfast omission. Ten healthy men (age 24 ± 1 yr) performed three trials in a randomized crossover order; omission and Low-GI (GI = 40) and High-GI (GI = 71) breakfast conditions. Middle cerebral artery velocity (transcranial Doppler ultrasonography) and arterial pressure (finger photoplethysmography) were continuously measured for 5 min before and 120 min following breakfast consumption to determine dCA using transfer function analysis. After these measurements of dCA, venous blood samples for the assessment of plasma BDNF were obtained. Moreover, blood glucose was measured before breakfast and every 30 min thereafter. The area under the curve of 2 h postprandial blood glucose in the High-GI trial was higher than the Low-GI trial (P < 0.01). The GI of the breakfast did not affect BDNF. In addition, both very-low (VLF) and low-frequency (LF) transfer function phase or gains were not changed during the omission trial. In contrast, LF gain (High-GI P < 0.05) and normalized gain (Low-GI P < 0.05) were decreased by both GI trials, while a decrease in VLF phase was observed in only the High-GI trial (P < 0.05). These findings indicate that breakfast consumption augmented dCA in the LF range but High-GI breakfast attenuated cerebral blood flow regulation against slow change (i.e., the VLF range) in arterial pressure. Thus we propose that breakfast and glycemic control may be an important strategy to optimize cerebrovascular health.
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Glucemia/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Desayuno , Circulación Cerebrovascular , Índice Glucémico , Arteria Cerebral Media/fisiología , Periodo Posprandial , Adulto , Factores de Edad , Biomarcadores/sangre , Estudios Cruzados , Homeostasis , Humanos , Insulina/sangre , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Factores Sexuales , Factores de Tiempo , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
NEW FINDINGS: What is the central question of this study? How does recurrent contact incurred across a season of professional rugby union impact molecular, cerebrovascular and cognitive function? What is the main findings and its importance? A single season of professional rugby union increases systemic oxidative-nitrosative stress (OXNOS) confirmed by a free radical-mediated suppression in nitric oxide bioavailability. Forwards encountered a higher frequency of contact events compared to backs, exhibiting elevated OXNOS and lower cerebrovascular function and cognition. Collectively, these findings provide mechanistic insight into the possible cause of reduced cognition in rugby union subsequent to impairment in the redox regulation of cerebrovascular function. ABSTRACT: Contact events in rugby union remain a public health concern. We determined the molecular, cerebrovascular and cognitive consequences of contact events during a season of professional rugby. Twenty-one male players aged 25 (mean) ± 4 (SD) years were recruited from a professional rugby team comprising forwards (n = 13) and backs (n = 8). Data were collected across the season. Pre- and post-season, venous blood was assayed for the ascorbate free radical (Aâ¢- , electron paramagnetic resonance spectroscopy) and nitric oxide (NO, reductive ozone-based chemiluminescence) to quantify oxidative-nitrosative stress (OXNOS). Middle cerebral artery velocity (MCAv, Doppler ultrasound) was measured to assess cerebrovascular reactivity (CVR), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Notational analysis determined contact events over the season. Forwards incurred more collisions (Mean difference [MD ] 7.49; 95% CI, 2.58-12.40; P = 0.005), tackles (MD 3.49; 95% CI, 0.42-6.56; P = 0.028) and jackals (MD 2.21; 95% CI, 0.18-4.24; P = 0.034). Forwards suffered five concussions while backs suffered one concussion. An increase in systemic OXNOS, confirmed by elevated Aâ¢- (F2,19 = 10.589, P = 0.004) and corresponding suppression of NO bioavailability (F2,19 = 11.492, P = 0.003) was apparent in forwards and backs across the season. This was accompanied by a reduction in cerebral oxygen delivery ( cDO2 , F2,19 = 9.440, P = 0.006) and cognition (F2,19 = 4.813, P = 0.041). Forwards exhibited a greater decline in the cerebrovascular reactivity range to changes in PETCO2 ( CVRCO2RANG compared to backs (MD 1.378; 95% CI, 0.74-2.02; P < 0.001).
Asunto(s)
Fútbol Americano , Adulto , Cognición , Fútbol Americano/fisiología , Humanos , Masculino , Arteria Cerebral Media , Oxidación-Reducción , RugbyRESUMEN
NEW FINDINGS: What is the central question of this study? To what extent do hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness? What is the main finding and its importance? We provide evidence for site-specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness. ABSTRACT: The aim of the present study was to determine the extent to which hypoxia-induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2 ), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2 ) and hypoxia (12% O2 ). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546-0.709, P = 0.004-0.043; Environmental Symptoms Questionnaires-Cerebral symptoms score, r = 0.587-0.771, P = 0.001-0.027, n = 4). Collectively, these findings highlight the site-specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.
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Mal de Altura , Enfermedad Aguda , Circulación Cerebrovascular/fisiología , Humanos , Hipoxia , Masculino , Oxígeno , Método Simple CiegoRESUMEN
Football players are at increased risk of neurodegeneration, the likely consequence of repetitive mechanical trauma caused by heading the ball. However, to what extent a history of heading the ball affects cerebral blood flow (CBF) regulation and its potential relationship to cognitive impairment is unknown. To address this, we recruited 16 concussion-free male amateur football players (age: 25 ± 6 y) with a history of heading the ball (18 ± 6 y) and 18 sex, age, education, and activity-matched controls with no prior history of contact sport participation or concussion. Cerebral perfusion was measured at rest and in response to both hyper/hypocapnia to determine cerebrovascular reactivity to carbon dioxide (CVRCO2HYPER/HYPO ) using transcranial Doppler ultrasound and capnography, with the sum reflecting the cerebral vasomotor range. Cognition and visuomotor coordination were assessed using the Montreal cognitive assessment (MoCA) and the Grooved Pegboard Dexterity Test (GPD), respectively. While no differences in cerebral perfusion were observed (p = 0.938), CVRCO2HYPER/HYPO (p = 0.038/p = 0.025), cerebral vasomotor range (p = 0.002), MoCA (p = 0.027), and GPD performance (dominant hand, P ≤ 0.001) were consistently lower in the players compared to controls. These findings are the first to demonstrate that CBF regulation and cognition are collectively impaired in male football players with history of heading the ball, which may contribute to neurodegeneration.
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Traumatismos en Atletas/fisiopatología , Conmoción Encefálica/fisiopatología , Circulación Cerebrovascular/fisiología , Trastornos del Conocimiento/fisiopatología , Fútbol/lesiones , Fútbol/fisiología , Adulto , Estudios Transversales , Humanos , Masculino , Adulto JovenRESUMEN
Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior-recurrent contact impacts molecular-hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13-19) years playing history reporting 3 (IQR 1-4) concussions. They were compared to 17 sex-age-physical activity-and education-matched non-contact controls with no prior history of self-reported concussion. Venous blood was assayed directly for the ascorbate free radical (Aâ¢- electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone-based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia ( CVR CO 2 Hyper / Hypo ). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative-nitrosative stress was confirmed in the players through increased Aâ¢- (p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range ( CVR CO 2 Range ; p = 0.045) elevation in neurofilament light-chain (p = 0.010) and frontotemporal impairments in immediate-memory (p = 0.001) delayed-recall (p = 0.048) and fine-motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior-recurrent contact and concussion history is associated with a free radical-mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.
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Conmoción Encefálica/fisiopatología , Conmoción Encefálica/psicología , Circulación Cerebrovascular , Trastornos del Conocimiento/etiología , Fútbol Americano/lesiones , Adulto , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Hemodinámica , Humanos , Masculino , Arteria Cerebral Media/fisiología , Óxido Nítrico/sangre , Estrés Oxidativo , Recurrencia , Factores de RiesgoRESUMEN
High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine arterial-venous differences across the brain for lactate (a-v difflactate), glucose (a-v diffglucose), oxygen (a-v diffoxygen), and brain-derived neurotrophic factor (BDNF; a-v diffBDNF). EF was evaluated by the color-word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a-v diffglucose was unchanged, whereas the a-v diffBDNF increased similarly after both HIIEs, and the a-v difflactate increased, but the increase was attenuated after the second HIIE, compared with the first HIIE ( P < 0.05). The EF after HIIE correlated with the a-v difflactate ( r2 = 0.62; P < 0.01). We propose that attenuated improvement in EF after repeated HIIE relates to reduced cerebral lactate metabolism and is, thereby, linked to systemic metabolism as an example of the lactate shuttle mechanism.-Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sørensen, H., Nielsen, H. B., Secher, N. H., Ogoh, S. Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men.
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Encéfalo/metabolismo , Ejercicio Físico/fisiología , Ácido Láctico/sangre , Adulto , Factor Neurotrófico Derivado del Encéfalo/sangre , Humanos , Masculino , Factores de TiempoRESUMEN
Gq/11 protein-coupled human histamine H1 receptors in Chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. In this study, we evaluated the effects of a sustained increase in intracellular Ca2+ concentrations induced by a receptor-bypassed stimulation with ionomycin, a Ca2+ ionophore, on the endocytosis and down-regulation of H1 receptors in Chinese hamster ovary cells. All cellular and cell-surface H1 receptors were detected by the binding of [3 H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H1 receptor ligands, mepyramine and pirdonium, respectively. The pretreatment of cells with ionomycin markedly reduced the mepyramine- and pirdonium-sensitive binding sites of [3 H]mepyramine, which were completely abrogated by the deprivation of extracellular Ca2+ and partially by a ubiquitin-activating enzyme inhibitor (UBEI-41), but were not affected by inhibitors of calmodulin (W-7 or calmidazolium) and protein kinase C (chelerythrine or GF109203X). These ionomycin-induced changes were also not affected by inhibitors of receptor endocytosis via clathrin (hypertonic sucrose) and caveolae/lipid rafts (filipin or nystatin) or by inhibitors of lysosomes (E-64, leupeptin, chloroquine, or NH4 Cl), proteasomes (lactacystin or MG-132), and a Ca2+ -dependent non-lysosomal cysteine protease (calpain) (MDL28170). Since H1 receptors were normally detected by confocal immunofluorescence microscopy with an antibody against H1 receptors, even after the ionomycin treatment, H1 receptors appeared to exist in a form to which [3 H]mepyramine was unable to bind. These results suggest that H1 receptors are apparently down-regulated by a sustained increase in intracellular Ca2+ concentrations with no process of endocytosis and lysosomal/proteasomal degradation of receptors.
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Señalización del Calcio/fisiología , Calcio/farmacología , Receptores Histamínicos H1/biosíntesis , Animales , Astrocitoma , Células CHO , Ionóforos de Calcio/farmacología , Señalización del Calcio/efectos de los fármacos , Calmodulina/antagonistas & inhibidores , Calpaína/antagonistas & inhibidores , Línea Celular Tumoral , Cricetinae , Cricetulus , Regulación hacia Abajo/efectos de los fármacos , Endocitosis/efectos de los fármacos , Histamina/farmacología , Humanos , Fosfatos de Inositol/metabolismo , Ionomicina/farmacología , Lisosomas/efectos de los fármacos , Microdominios de Membrana/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Pirilamina/metabolismo , Receptores Histamínicos H1/genética , Proteínas Recombinantes/biosíntesisRESUMEN
Arterial baroreflex function is important for blood pressure control during exercise, but its contribution to cardiovascular adjustments at the onset of cycling exercise remains unclear. Fifteen healthy male subjects (24 ± 1 yr) performed 45-s trials of low- and moderate-intensity cycling, with carotid baroreceptor stimulation by neck suction at -60 Torr applied 0-5, 10-15, and 30-35 s after the onset of exercise. Cardiovascular responses to neck suction during cycling were compared with those obtained at rest. An attenuated reflex decrease in heart rate following neck suction was detected during moderate-intensity exercise, compared with the response at rest (P < 0.05). Furthermore, compared with the reflex decrease in blood pressure elicited at rest, neck suction elicited an augmented decrease in blood pressure at 0-5 and 10-15 s during low-intensity exercise and in all periods during moderate-intensity exercise (P < 0.05). The reflex depressor response at the onset of cycling was primarily mediated by an increase in the total vascular conductance. These findings evidence altered carotid baroreflex function during the first 35 s of cycling compared with rest, with attenuated bradycardic response, and augmented depressor response to carotid baroreceptor stimulation.
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Barorreflejo/fisiología , Ciclismo/fisiología , Presión Sanguínea/fisiología , Seno Carotídeo/fisiología , Esfuerzo Físico/fisiología , Presorreceptores/fisiología , Adulto , Seno Carotídeo/inervación , Humanos , MasculinoRESUMEN
PURPOSE: We evaluated whether repeated high-intensity interval exercise (HIIE) influences plasma oxytocin (OT) concentration in healthy men, and, given that OT is mainly synthesized in the hypothalamus, we assessed the concentration difference between the arterial (OT ART ) versus the internal jugular venous OT concentration (OT IJV ). Additionally, we hypothesized that an increase in cerebral OT release and the circulating concentration would be augmented by repeated HIIE. METHODS: Fourteen healthy men (age = 24 ± 2 yr; mean ± SD) performed two identical bouts of HIIE. These HIIE bouts included a warm-up at 50%-60% maximal workload ( Wmax ) for 5 min followed by four bouts of exercise at 80%-90% Wmax for 4 min interspersed by exercise at 50%-60% Wmax for 3 min. The HIIE bouts were separated by 60 min of rest. OT was evaluated in blood through radial artery and internal jugular vein catheterization. RESULTS: Both HIIE bouts increased both OT ART (median [IQR], from 3.9 [3.4-5.4] to 5.3 [4.4-6.3] ng·mL -1 in the first HIIE, P < 0.01) and OT IJV (from 4.6 [3.4-4.8] to 5.9 [4.3-8.2] ng·mL -1 , P < 0.01), but OT ART-IJV was unaffected (from -0.24 [-1.16 to 1.08] to 0.04 [-0.88 to 0.78] ng·mL -1 , P = 1.00). The increased OT levels were similar in the first and second HIIE bouts (OT ARTP = 0.25, OT IJVP = 0.36). CONCLUSIONS: Despite no change in the cerebral OT release via the internal jugular vein, circulating OT increases during HIIE regardless of the accumulated exercise volume, indicating that OT may play role as one of the exerkines.
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Entrenamiento de Intervalos de Alta Intensidad , Oxitocina , Adulto , Humanos , Masculino , Adulto Joven , Ejercicio Físico/fisiología , Oxitocina/sangre , Ejercicio de CalentamientoRESUMEN
PURPOSE: No study has assessed the acute effect of caffeine supplementation on 100-m sprint running in athletics and caffeine's net ergogenicity on 100-m sprint running remains unclear. We investigated the acute effects of caffeine supplementation on 100-m sprint running performance in a field test. METHODS: Thirteen male collegiate sprinters were subjected to 100-m sprint running time trials (TT) after the ingestion of 6 mg·kg -1 body weight caffeine or placebo supplementation in a double-blind, counterbalanced, randomized, and crossover design. Sprint velocity was measured with a laser system, and sprint time was calculated from the data in which the effects of environmental factors that would act as confounding factors on sprint time during TT were eliminated. RESULTS: The corrected 100-m sprint time was significantly shortened by 0.14 s with caffeine supplementation compared with placebo (placebo: 11.40 ± 0.39 s, caffeine: 11.26 ± 0.33 s; P = 0.007, g = -0.33). The corrected sprint time up to 60 m during TT was also significantly shorter with caffeine supplementation than with placebo ( P = 0.002). Furthermore, the mean sprint velocity for splits of 0-10 and 10-20 m was significantly increased by caffeine supplementation (all P < 0.05). CONCLUSIONS: Acute caffeine supplementation enhanced the corrected 100-m sprint time by improving the sprint performance in the first 60 m after more explosive acceleration in the early stage of the acceleration phase. Thus, for the first time, we directly demonstrated caffeine's ergogenicity on 100-m sprint performance in athletics.
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Rendimiento Atlético , Carrera , Humanos , Masculino , Cafeína/farmacología , Suplementos Dietéticos , Método Doble Ciego , Estudios CruzadosRESUMEN
We aimed to evaluate the blood lactate level in response to two bouts of exercise. First, we hypothesized that blood lactate elevation in response to moderate-intensity aerobic exercise (MIAE) would be lower at the end of the second bout of MIAE than the first bout of MIAE. In this context, we also hypothesized that lactate accumulation at the end of resistance exercise (RE) would be reduced if MIAE is performed before RE (i.e., concurrent exercise; CE). If so, we hypothesized that the order of the CE (i.e., RE + MIAE vs. MIAE + RE) influences blood lactate kinetics. To test the hypotheses, forty-three healthy men participated in three studies. In study 1, 20 men (age 21 ± 2 years) performed two bouts of a 20-min MIAE separated by a 20-min rest interval. In study 2, 11 men (age 22 ± 1 years) performed RE only and CE (MIAE + RE; ARCE) with a 20-min rest interval in a crossover design. In study 3, 12 men (age 21 ± 2 years) performed both CEs, which were ARCE and RE + MIAE (RACE), with a 20-min rest interval in a crossover design. We measured blood lactate before and at the end of each exercise session. In study 1, the blood lactate response to the second bout of MIAE was lower than that of the first bout (P < 0.001, r = 0.68). However, the blood lactate response to the ARCE trial was not lower than the response to the RE trial in study 2 (P = 0.475, r = 0.22). The results of study 3 showed that the RACE and ARCE trials induced a similar lactate response (MIAE P = 0.423, r = 0.28; RE P = 0.766, d = 0.03). These observations indicate that whereas lactate accumulation might be diminished by a second bout of MIAE, a different type of exercise (i.e., aerobic/resistance) did not result in a diminished lactate accumulation in response to a second bout of exercise.
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Ácido Láctico , Consumo de Oxígeno , Humanos , Masculino , Adulto Joven , Ejercicio Físico/fisiología , Prueba de Esfuerzo , Terapia por Ejercicio , Extremidad Inferior , Consumo de Oxígeno/fisiología , Estudios CruzadosRESUMEN
Aerobic exercise acutely improves cognitive function (e.g., executive function (EF); memory recognition (MR)) and increases circulating brain-derived neurotrophic factor (BDNF). In addition, branched-chain amino acids (BCAA) ingestion acutely shortens the choice reaction time and increases brain BDNF. We examined whether the ingestion of essential amino acid (EAA) supplements (mainly composed of BCAA) would positively impact on cognitive function and circulating BDNF after moderate-intensity aerobic exercise. Twenty-two healthy young men received either an EAA supplements or the placebo (PL) 30 min before undergoing aerobic exercise. The participants performed a cycling exercise at 60% of peak oxygen uptake for 30 min. EF after aerobic exercise was better after the EAA treatment than after the PL treatment (P = 0.02). MR (P = 0.38 for response accuracy; P = 0.15 for reaction time) and circulating BDNF (P = 0.59) were not altered by EAA supplements. EF improvement was correlated with increases in some amino acids (leucine, isoleucine, valine, lysine, phenylalanine; all Ps < 0.05) that are potential substrates for synthesizing neurotransmitters in the brain. These results suggest that EAA supplements ingestion had a positive effect on EF after moderate-intensity aerobic exercise, while MR and BDNF were not altered.
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Factor Neurotrófico Derivado del Encéfalo , Función Ejecutiva , Masculino , Humanos , Aminoácidos Esenciales , Aminoácidos de Cadena Ramificada , Ejercicio Físico/fisiología , Ingestión de AlimentosRESUMEN
The speed and accuracy of decision-making (i.e., executive function (EF) domains) is an integral factor in many sports. At rest, prolonged cognitive load (pCL) impairs reaction time (RT). In contrast, exercise improves RT and EF. We hypothesized that RT and EF during exercise would be diminished by prolonged 'dual tasking' as a consequence of pCL. To test the hypothesis, twenty healthy male participants performed four conditions [resting control (Rest), pCL only (pCLRest), exercise only (EX), and pCL + exercise (pCLEX)] in a randomized-crossover design. Both exercise conditions utilized a 50-min cycling exercise protocol (60% VO2 peak) and the pCL was achieved via a 50-min colour-word Stroop task (CWST). Compared with Rest, pCLRest caused a slowed CWST RT (P < 0.05) and a large SD (i.e., intraindividual variability) of CWST RT (P < 0.01). Similarly, compared with EX, the slowed CWST RT (P < 0.05) and large SD of CWST RT (P < 0.01) were also observed in pCLEX. Whereas the reverse-Stroop interference was not affected in pCLRest (P = 0.46), it was larger (i.e., declined EF) in pCLEX than EX condition (P < 0.05). These observations provide evidence that the effort of pCL impairs RT and EF even during exercise.
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Función Ejecutiva , Ejercicio Físico , Humanos , Masculino , Ejercicio Físico/psicología , Tiempo de Reacción , Test de Stroop , CogniciónRESUMEN
Emergent evidence suggests that cyclic intermittent hypoxia increases cerebral arterial shear rate and endothelial function, whereas continuous exposure decreases anterior cerebral oxygen (O2) delivery. To examine to what extent continuous hypoxia impacts cerebral shear rate, cerebral endothelial function, and consequent cerebral O2 delivery (CDO2), eight healthy males were randomly assigned single-blind to 7 h passive exposure to both normoxia (21% O2) and hypoxia (12% O2). Blood flow in the brachial and internal carotid arteries were determined using Duplex ultrasound and included the combined assessment of systemic and cerebral endothelium-dependent flow-mediated dilatation. Systemic (brachial artery) flow-mediated dilatation was consistently lower during hypoxia (P = 0.013 vs. normoxia), whereas cerebral flow-mediated dilation remained preserved (P = 0.927 vs. normoxia) despite a reduction in internal carotid artery antegrade shear rate (P = 0.002 vs. normoxia) and CDO2 (P < 0.001 vs. normoxia). Collectively, these findings indicate that the reduction in CDO2 appears to be independent of cerebral endothelial function and contrasts with that observed during cyclic intermittent hypoxia, highlighting the regulatory importance of (hypoxia) dose duration and flow/shear rate phenotype.
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Hipoxia , Vasodilatación , Dilatación , Humanos , Masculino , Oxígeno , Fenotipo , Método Simple Ciego , Vasodilatación/fisiologíaRESUMEN
It has been well established in epidemiological studies and randomized controlled trials that habitual exercise is beneficial for brain health, such as cognition and mental health. Generally, it may be reasonable to say that the physiological benefits of acute exercise can prevent brain disorders in late life if such exercise is habitually/chronically conducted. However, the mechanisms of improvement in brain function via chronic exercise remain incompletely understood because such mechanisms are assumed to be multifactorial, such as the adaptation of repeated acute exercise. This review postulates that cerebral metabolism may be an important physiological factor that determines brain function. Among metabolites, the provision of lactate to meet elevated neural activity and regulate the cerebrovascular system and redox states in response to exercise may be responsible for exercise-enhanced brain health. Here, we summarize the current knowledge regarding the influence of exercise on brain health, particularly cognitive performance, with the underlying mechanisms by means of lactate. Regarding the influence of chronic exercise on brain function, the relevance of exercise intensity and modality, particularly high-intensity interval exercise, is acknowledged to induce "metabolic myokine" (i.e., lactate) for brain health.