RESUMEN
Central adiposity is associated with greater sympathetic support of blood pressure. ß-adrenergic receptors (ß-AR) buffer sympathetically mediated vasoconstriction and ß-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized ß-AR vasodilation would be lower in obese compared with normal weight adults. Because ß-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to ß-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (ΔFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [NG-monomethyl-l-arginine (l-NMMA)], COX (ketorolac), and NOS + COX (l-NMMA + ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). l-NMMA attenuated Iso-mediated ΔFVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased Iso-mediated ΔFVC (P < 0.01) and this response was lost with concurrent l-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac + l-NMMA (P = 0.40) altered Iso-mediated ΔFVC in adults with obesity. Despite shifts in COX and NOS, ß-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity.NEW & NOTEWORTHY We examined ß-adrenergic receptor-mediated vasodilation in skeletal muscle of humans with obesity and normal weight. Results show that despite shifts in the contribution of cyclooxygenase and nitric oxide synthase, ß-adrenergic-mediated vasodilation is relatively preserved in young, otherwise healthy adults with obesity. These data highlight the presence of subclinical changes in microvascular control mechanisms early in the obesity process and suggest duration of obesity and/or the addition of primary aging may be necessary for overt dysfunction.
Asunto(s)
Músculo Esquelético/irrigación sanguínea , Óxido Nítrico Sintasa de Tipo III/metabolismo , Obesidad/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Vasodilatación , Agonistas Adrenérgicos beta/farmacología , Adulto , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiología , Inhibidores de la Ciclooxigenasa/farmacología , Femenino , Humanos , Isoproterenol/farmacología , Ketorolaco/farmacología , Masculino , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Obesidad/fisiopatología , Receptores Adrenérgicos beta/metabolismo , omega-N-Metilarginina/farmacologíaRESUMEN
Peripheral artery disease (PAD) is a vascular pathology with high prevalence among the aging population. PAD is associated with decreased cognitive performance, but the underlying mechanisms remain obscure. Normal brain function critically depends on an adequate adjustment of cerebral blood supply to match the needs of active brain regions via neurovascular coupling (NVC). NVC responses depend on healthy microvascular endothelial function. PAD is associated with significant endothelial dysfunction in peripheral arteries, but its effect on NVC responses has not been investigated. This study was designed to test the hypothesis that NVC and peripheral microvascular endothelial function are impaired in PAD. We enrolled 11 symptomatic patients with PAD and 11 age- and sex-matched controls. Participants were evaluated for cognitive performance using the Cambridge Neuropsychological Test Automated Battery and functional near-infrared spectroscopy to assess NVC responses during the cognitive n-back task. Peripheral microvascular endothelial function was evaluated using laser speckle contrast imaging. We found that cognitive performance was compromised in patients with PAD, evidenced by reduced visual memory, short-term memory, and sustained attention. We found that NVC responses and peripheral microvascular endothelial function were significantly impaired in patients with PAD. A positive correlation was observed between microvascular endothelial function, NVC responses, and cognitive performance in the study participants. Our findings support the concept that microvascular endothelial dysfunction and neurovascular uncoupling contribute to the genesis of cognitive impairment in older PAD patients with claudication. Longitudinal studies are warranted to test whether the targeted improvement of NVC responses can prevent or delay the onset of PAD-associated cognitive decline.NEW & NOTEWORTHY Peripheral artery disease (PAD) was associated with significantly decreased cognitive performance, impaired neurovascular coupling (NVC) responses in the prefrontal cortex (PFC), left and right dorsolateral prefrontal cortices (LDLPFC and RDLPFC), and impaired peripheral microvascular endothelial function. A positive correlation between microvascular endothelial function, NVC responses, and cognitive performance may suggest that PAD-related cognitive decrement is mechanistically linked, at least in part, to generalized microvascular endothelial dysfunction and subsequent impairment of NVC responses.
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Disfunción Cognitiva , Acoplamiento Neurovascular , Enfermedad Arterial Periférica , Anciano , Envejecimiento/fisiología , Arteriolas , Circulación Cerebrovascular/fisiología , Humanos , Acoplamiento Neurovascular/fisiologíaRESUMEN
The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region-specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L-NMMA, administered in a randomized, single-blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L-NMMA (or volume-matched saline) was infused intravenously for 5 min prior to imaging. L-NMMA reduced CBF (L-NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5-7%) in anterior and posterior cerebral circulations, due in part to the reduced cross-sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L-NMMA (L-NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7-11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. KEY POINTS: Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear. Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously. Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L-NMMA) reduced CBF by up to 11% in different brain regions. NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling.
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Circulación Cerebrovascular , Óxido Nítrico Sintasa , Flujo Sanguíneo Regional , omega-N-Metilarginina , Adulto , Femenino , Humanos , Masculino , Óxido Nítrico , Óxido Nítrico Sintasa/antagonistas & inhibidores , Perfusión , Método Simple Ciego , Adulto Joven , omega-N-Metilarginina/farmacologíaRESUMEN
Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation (SpO2)]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% (P < 0.001) and artery CSA (P < 0.001), which was similar across arteries. Hypoxia (SpO2 80%-83%) increased CVC (P < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/-ΔSpO2) across arteries (P < 0.05), in part because of increases in CSA (P < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/ΔSpO2 to hypoxia. These findings indicate that 1) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and 2) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries.
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Arterias Cerebrales/enzimología , Circulación Cerebrovascular , Hipoxia/enzimología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Vasodilatación , Adulto , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Hipoxia/sangre , Hipoxia/diagnóstico por imagen , Hipoxia/fisiopatología , Indometacina/administración & dosificación , Masculino , Oxígeno/sangre , Distribución Aleatoria , Vasodilatación/efectos de los fármacos , Adulto JovenRESUMEN
KEY POINTS: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Near-infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation. Here we compared a combined NIRS-DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS-derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level. We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. ABSTRACT: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Combining DCS with near-infrared spectroscopy (NIRS) introduces exciting possibilities for understanding the determinants of muscle oxygen consumption; however, no investigation has directly compared NIRS-DCS to conventional measures of oxygen delivery and utilization in an exercising limb. To address this knowledge gap, nine healthy males performed rhythmic handgrip exercise with simultaneous measurements by NIRS-DCS, Doppler blood flow and venous oxygen content. The two approaches showed good concurrent validity, with directionally similar responses between: (a) Doppler-derived forearm blood flow and DCS-derived blood flow index (BFI), and (b) venous oxygen saturation and NIRS-derived tissue saturation. To explore the utility of combined NIRS-DCS across the physiological spectrum, we manipulated forearm arterial perfusion pressure by altering the arm position above or below the level of the heart. As expected, Doppler-derived skeletal muscle blood flow increased with exercise in both arm positions, but with markedly different magnitudes (below: +424.3 ± 41.4 ml/min, above: +306 ± 12.0 ml/min, P = 0.002). In contrast, DCS-derived microvascular BFI increased to a similar extent with exercise, regardless of arm position (P = 0.65). Importantly, however, the time to reach BFI steady state was markedly slower with the arm above the heart, supporting the experimental design. Notably, we observed faster tissue desaturation at the onset of exercise with the arm above the heart, resulting in similar muscle oxygen consumption profiles throughout exercise. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of skeletal muscle oxygen utilization non-invasively and throughout exercise.
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Fuerza de la Mano/fisiología , Músculo Esquelético/fisiología , Consumo de Oxígeno , Adulto , Arteria Braquial/fisiología , Ejercicio Físico/fisiología , Antebrazo/irrigación sanguínea , Antebrazo/fisiología , Humanos , Masculino , Músculo Esquelético/irrigación sanguínea , Flujo Sanguíneo Regional , Espectroscopía Infrarroja Corta , Adulto JovenRESUMEN
We tested the hypothesis that women exhibit greater vasodilator responses to ß-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to ß-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (ß-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [N(G)-monomethyl-l-arginine (l-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P < 0.01), and this effect was not different between men and women (P = 0.41). l-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P > 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men (P < 0.01) and women (P = 0.04) and this rise was lost with subsequent l-NMMA infusion (men, P < 0.01; women, P < 0.05). ß-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to ß-mediated vasodilation are not present. However, these data are the first to demonstrate ß-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores Enzimáticos/farmacología , Isoproterenol/farmacología , Ketorolaco/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Vasodilatación/efectos de los fármacos , omega-N-Metilarginina/farmacología , Adulto , Femenino , Antebrazo/irrigación sanguínea , Humanos , Infusiones Intraarteriales , Masculino , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Prostaglandina-Endoperóxido Sintasas/fisiología , Factores Sexuales , Ultrasonografía Doppler , Vasodilatación/fisiologíaRESUMEN
PURPOSE: We hypothesized exercise vasodilation would be greater in women due to nitric oxide synthase (NOS) and cyclooxygenase (COX) signaling. METHODS: 45 healthy adults (23 women, W, 22 men, M, 26 ± 1 years) completed two 10-min trials of dynamic forearm exercise at 15 % intensity. Forearm blood flow (FBF; Doppler ultrasound), arterial pressure (brachial catheter), and forearm lean mass were measured to calculate relative forearm vascular conductance (FVCrel) = FBF 100 mmHg(-1) 100 g(-1) lean mass. Local intra-arterial infusion of L-NMMA or ketorolac acutely inhibited NOS and COX, respectively. In Trial 1, the first 5 min served as control exercise (CON), followed by 5 min of L-NMMA or ketorolac over the last 5 min of exercise. In Trial 2, the remaining drug was infused during 5-10 min, to achieve combined NOS-COX inhibition (double blockade, DB). RESULTS: Are mean ± SE. Women exhibited 29 % greater vasodilation in CON (ΔFVCrel, 19 ± 1 vs. 15 ± 1, p = 0.01). L-NMMA reduced ΔFVCrel (p < 0.001) (W: Δ -2.3 ± 1.3 vs. M: Δ -3.7 ± 0.8, p = 0.25); whereas, ketorolac modestly increased ΔFVCrel (p = 0.04) similarly between sexes (W: Δ 1.6 ± 1.1 vs. M: Δ 2.0 ± 1.6, p = 0.78). DB was also found to be similar between the sexes (p = 0.85). CONCLUSION: These data clearly indicate women produce a greater exercise vasodilator response. Furthermore, contrary to experiments in animal models, these data are the first to demonstrate vascular control by NOS and COX is similar between sexes.
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Ejercicio Físico/fisiología , Óxido Nítrico Sintasa/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Vasodilatación/fisiología , Adolescente , Adulto , Inhibidores de la Ciclooxigenasa/farmacología , Inhibidores Enzimáticos/farmacología , Femenino , Antebrazo/diagnóstico por imagen , Antebrazo/fisiología , Hemodinámica/fisiología , Humanos , Ketorolaco/farmacología , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Flujo Sanguíneo Regional/fisiología , Caracteres Sexuales , Ultrasonografía , Resistencia Vascular/fisiología , Vasodilatación/efectos de los fármacos , Adulto Joven , omega-N-Metilarginina/farmacologíaRESUMEN
We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = -0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.
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Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Arteria Braquial/efectos de los fármacos , Ejercicio Físico , Antebrazo/irrigación sanguínea , Síndrome Metabólico/fisiopatología , Obesidad/fisiopatología , Vasodilatación/efectos de los fármacos , Adolescente , Adulto , Presión Arterial , Biomarcadores/sangre , Velocidad del Flujo Sanguíneo , Arteria Braquial/fisiopatología , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Mediadores de Inflamación/sangre , Infusiones Intraarteriales , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Obesidad/sangre , Obesidad/diagnóstico , Flujo Sanguíneo Regional , Factores de Tiempo , Adulto JovenRESUMEN
Electroencephalography (EEG) allows for the evaluation of real time changes in brain (electrocortical) activity during exercise. A few studies have examined changes in electrocortical activity using stationary cycling, but the findings have been mixed. Some of these studies have found increases in brain activity following exercise, while others have found decreases in brain activity following exercise. Hence, it is of importance to identify post-exercise changes in brain activity. Sixteen healthy, untrained subjects (8 males; 8 females) participated in the study. All 16 participants performed a graded exercise test (GXT) to volitional exhaustion on an upright cycle ergometer. Continuous EEG recordings were sampled before (PRE) and immediately following (IP) the GXT. Regions of interest were primarily the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), and left and right motor cortex (MC). In the DLPFC, a frontal asymmetry index was also identified. There was a statistically significant increase in theta power in the DLPFC, VLPFC, and left and right MC from PRE to IP (all p < 0.05). There was also a shift towards right hemisphere asymmetry at the IP time point in the DLPFC (p < 0.05). Finally, there was an increase in alpha power from PRE to IP in the right MC (p < 0.05). EEG could prove to be an important way to measure the effects of central fatigue on brain activity before and immediately following exercise.
RESUMEN
A monoexponential model characterizing cerebral blood velocity dynamics at the onset of exercise may mask dynamic responses by the cerebrovasculature countering large fluctuations of middle cerebral artery blood velocity (MCAv) and cerebral perfusion pressure (CPP) oscillations. Therefore, the purpose of this study was to determine whether the use of a monoexponential model attributes initial fluctuations of MCAv at the start of exercise as a time delay (TD). Twenty-three adults (10 women, 23.9 ± 3.3 yrs; 23.7 ± 2.4 kg/m2 ) completed 2 min of rest followed by 3 mins of recumbent cycling at 50 W. MCAv, CPP, and Cerebrovascular Conductance index (CVCi), calculated as CVCi = MCAv/MAP × 100 mmHg, were collected, a lowpass filter (0.2 Hz) was applied, and averaged into 3-second bins. MCAv data were then fit to a monoexponential model [ΔMCAv(t) = Amp(1 - e-(t-TD)/τ )]. TD, tau (τ), and mean response time (MRT = TD + τ) were obtained from the model. Subjects exhibited a TD of 20.2 ± 18.1 s. TD was directly correlated with MCAv nadir (MCAvN ), r = -0.560, p = 0.007, which occurred at similar times (16.5 ± 15.3 vs. 20.2 ± 18.1 s, p = 0.967). Regressions indicated CPP as the strongest predictor of MCAvN ( R a 2 $$ {R}_a^2 $$ = 0.36). Fluctuations in MCAv were masked using a monoexponential model. To adequately understand cerebrovascular mechanisms during the transition from rest to exercise, CPP and CVCi must also be analyzed. A concurrent drop in cerebral perfusion pressure and middle cerebral artery blood velocity at the start of exercise forces the cerebrovasculature to respond to maintain cerebral blood flow. The use of a monoexponential model characterizes this initial phase as a time delay and masks this large important response.
Asunto(s)
Circulación Cerebrovascular , Ejercicio Físico , Adulto , Humanos , Femenino , Velocidad del Flujo Sanguíneo/fisiología , Ejercicio Físico/fisiología , Circulación Cerebrovascular/fisiología , Arteria Cerebral Media/fisiología , Descanso , Presión Sanguínea/fisiologíaRESUMEN
Ninety-million Americans suffer metabolic syndrome (MetSyn), increasing the risk of diabetes and poor brain outcomes, including neuropathology linked to lower cerebral blood flow (CBF), predominantly in anterior regions. We tested the hypothesis that total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. Thirty-four controls (25 ± 5 yr) and 19 MetSyn (30 ± 9 yr), with no history of cardiovascular disease/medications, underwent four-dimensional flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, whereas arterial spin labeling quantified brain perfusion in a subset (n = 38/53). Contributions of cyclooxygenase (COX; n = 14), nitric oxide synthase (NOS, n = 17), or endothelin receptor A signaling (n = 13) were tested with indomethacin, NG-monomethyl-L-arginine (L-NMMA), and Ambrisentan, respectively. Total CBF was 20 ± 16% lower in MetSyn (725 ± 116 vs. 582 ± 119 mL/min, P < 0.001). Anterior and posterior brain regions were 17 ± 18% and 30 ± 24% lower in MetSyn; reductions were not different between regions (P = 0.112). Global perfusion was 16 ± 14% lower in MetSyn (44 ± 7 vs. 36 ± 5 mL/100 g/min, P = 0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P = 0.004) was not different between groups (P = 0.244, n = 14, 3), and Ambrisentan had no effect on either group (P = 0.165, n = 9, 4). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P = 0.041), but CBF decrease in posterior was not different between groups (P = 0.151, n = 8, 6). These data indicate that adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.NEW & NOTEWORTHY We tested the impact of insulin resistance (IR) on resting cerebral blood flow (CBF) in adults with metabolic syndrome (MetSyn). Using MRI and research pharmaceuticals to study the role of NOS, ET-1, or COX signaling, we found that adults with MetSyn exhibit substantially lower CBF that is not explained by changes in NOS or ET-1 signaling. Interestingly, adults with MetSyn show a loss of COX-mediated vasodilation in the anterior but not posterior circulation.
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Síndrome Metabólico , Humanos , Adulto Joven , omega-N-Metilarginina , Indometacina , Circulación Cerebrovascular/fisiologíaRESUMEN
Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) (3 sets 10 reps 70% 1 repetition maximum (1RM), 5 exercises) and a bout of whole-body vibration (WBV) (5 sets 1 min bouts 20Hz 3.38mm peak to peak displacement, Vibraflex vibration platform). DXA was used to measure body composition and areal bone mineral density (aBMD) of the total body, AP lumbar spine, and dual proximal femur. pQCT was used to measure tibia bone characteristics (4%, 38%, 66% sites). Blood samples were collected before exercise (Pre), immediately-post (IP), 60 minutes post (60P), 24 hours (24H), and 48 hours (48H) after exercise to measure serum miR-21-5p, -23a-3p, -133a-3p, -148a-3p (qPCR) and TRAP5b (ELISA). There was a significant modality × time interaction for c-miR-21-5p expression (p=0.019), which decreased from 60P to 24H after WBV only. TRAP5b serum concentrations significantly increased IP then decreased below Pre at 24H for both WBV and RE (p<0.01). Absolute changes in TRAP5b were negatively correlated with c-miR-21-5p fold changes (r= -0.642 to -0.724, p<0.05) for both exercise modalities. There were significant negative correlations between baseline c-miRNAs and bone status variables (r= -0.639 to -0.877, p<0.05). Our findings suggest that whole-body vibration is a sufficient mechanical stimulus for altering c-miR-21-5p expression, whereas a high intensity resistance exercise protocol did not elicit any c-miRNA responses in postmenopausal women. Increases in the bone resorption marker, TRAP5b, were associated with greater downregulation of c-miR-21-5p expression.
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MicroARN Circulante , MicroARNs , Entrenamiento de Fuerza , Humanos , Femenino , Vibración , Posmenopausia , Ejercicio Físico/fisiología , MicroARNs/genéticaRESUMEN
The purpose of this study was to examine age-related differences in muscle performance in women divided into young (YW, 20-39 years, n = 29) middle-aged (MAW, 40-59 years, n = 33), and older (OW, ≥60 years, n = 40) age groups. METHODS: Hand grip strength, vertical jump performance, and knee extensor (KE) strength (0 deg/s, 60 deg/s, and 240 deg/s), speed of movement (SoM; at 1 Nm, 20%, 40%, and 60% isometric strength), and endurance (30-repetition test at 60 degs/s and 240 deg/s) were assessed. Computed tomography-acquired muscle cross-sectional area (mCSA) was measured and included to determine specific strength (KE strength/mCSA). RESULTS: Hand grip strength was similar across groups, while jump performance declined with age (YW and MAW > OW, p < 0.001). KE strength declined significantly with age (all conditions p < 0.01), while specific strength was similar across groups. SoM was significantly higher for YW and MAW compared to OW (both p < 0.01). An age × velocity interaction revealed YW KE endurance was similar between conditions, whereas MAW and OW displayed significantly better endurance during the 60 deg/s condition. OW displayed impaired KE endurance at 240 deg/s (vs. YW and MAW, p < 0.01) but improved at 60 deg/s (vs. YW, p < 0.01). Dynamic torque decline increased with age (YW < OW, p = 0.03) and was associated with intramuscular adipose tissue (r = 0.21, p = 0.04). CONCLUSIONS: Performance declines were most evident among OW, but few performance deficits had emerged in MAW. Interestingly, strength declines disappeared after normalizing to mCSA and endurance appears to be velocity-dependent.
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Envejecimiento , Fuerza de la Mano , Adulto , Femenino , Humanos , Rodilla , Persona de Mediana Edad , Fuerza Muscular , Músculo Esquelético , Adulto JovenRESUMEN
Understanding how the brain allocates resources to match the demands of active neurons under physiological conditions is critically important. Increased metabolic demands of active brain regions are matched with hemodynamic responses known as neurovascular coupling (NVC). Several methods that allow noninvasive assessment of brain activity in humans detect NVC and early detection of NVC impairment may serve as an early marker of cognitive impairment. Therefore, non-invasive NVC assessments may serve as a valuable tool to detect early signs of cognitive impairment and dementia. Working memory tasks are routinely employed in the evaluation of cognitive task-evoked NVC responses. However, recent attempts that utilized functional near-infrared spectroscopy (fNIRS) or transcranial Doppler sonography (TCD) while using a similar working memory paradigm did not provide convincing evidence for the correlation of the hemodynamic variables measured by these two methods. In the current study, we aimed to compare fNIRS and TCD in their performance of differentiating NVC responses evoked by different levels of working memory workload during the same working memory task used as cognitive stimulation. Fourteen healthy young individuals were recruited for this study and performed an n-back cognitive test during TCD and fNIRS monitoring. During TCD monitoring, the middle cerebral artery (MCA) flow was bilaterally increased during the task associated with greater cognitive effort. fNIRS also detected significantly increased activation during a more challenging task in the left dorsolateral prefrontal cortex (DLPFC), and in addition, widespread activation of the medial prefrontal cortex (mPFC) was also revealed. Robust changes in prefrontal cortex hemodynamics may explain the profound change in MCA blood flow during the same cognitive task. Overall, our data support our hypothesis that both TCD and fNIRS methods can discriminate NVC evoked by higher demand tasks compared to baseline or lower demand tasks.
Asunto(s)
Cognición , Acoplamiento Neurovascular , Adulto , Femenino , Hemodinámica , Humanos , Masculino , Memoria a Corto Plazo , Arteria Cerebral Media/diagnóstico por imagen , Arteria Cerebral Media/fisiología , Corteza Prefrontal/irrigación sanguínea , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiologíaRESUMEN
Sleep deprivation (SD) is a common condition and an important health concern. In addition to metabolic and cardiovascular risks, SD associates with decreases in cognitive performance. Neurovascular coupling (NVC, "functional hyperemia") is a critical homeostatic mechanism, which maintains adequate blood supply to the brain during periods of intensive neuronal activity. To determine whether SD alters NVC responses and cognitive performance, cognitive and hemodynamic NVC assessments were conducted prior to and 24 h post-SD in healthy young male individuals (n = 10, 27 ± 3 years old). Cognition was evaluated with a battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Hemodynamic components of NVC were measured by transcranial Doppler sonography (TCD) during cognitive stimulation, dynamic retinal vessel analysis (DVA) during flicker light stimulation, and functional near infrared spectroscopy (fNIRS) during finger tapping motor task. Cognitive assessments revealed impairments in reaction time and sustained attention after 24 h of SD. Functional NIRS analysis revealed that SD significantly altered hemodynamic responses in the prefrontal cortex and somatosensory cortex during a motor task. NVC-related vascular responses measured by DVA and TCD did not change significantly. Interestingly, TCD detected decreased task-associated cerebral blood flow (CBF) in the right middle cerebral artery in sleep deprived participants. Our results demonstrate that 24 h of SD lead to impairments in cognitive performance together with altered CBF and hemodynamic components of cortical NVC responses.
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Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Circulación Cerebrovascular , Cognición , Hemodinámica , Acoplamiento Neurovascular , Privación de Sueño/complicaciones , Adulto , Estudios de Casos y Controles , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/fisiopatología , Femenino , Humanos , Masculino , Neuronas/metabolismo , Tiempo de Reacción , Espectroscopía Infrarroja Corta , Ultrasonografía Doppler Transcraneal , Adulto JovenRESUMEN
Although systemic sex-specific differences in cardiovascular responses to exercise are well established, the comparison of sex-specific cerebrovascular responses to exercise has gone under-investigated especially, during high intensity exercise. Therefore, our purpose was to compare cerebrovascular responses in males and females throughout a graded exercise test (GXT). Twenty-six participants (13 Females and 13 Males, 24 ± 4 yrs.) completed a GXT on a recumbent cycle ergometer consisting of 3-min stages. Each sex completed 50W, 75W, 100W stages. Thereafter, power output increased 30W/stage for females and 40W/stage for males until participants were unable to maintain 60-80 RPM. The final stage completed by the participant was considered maximum workload(Wmax ). Respiratory gases (End-tidal CO2 , EtCO2 ), middle cerebral artery blood velocity (MCAv), heart rate (HR), non-invasive mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were continuously recorded on a breath-by-breath or beat-by-beat basis. Cerebral perfusion pressure, CPP = MAP (0. 7,355 distance from heart-level to doppler probe) and cerebral vascular conductance index, CVCi = MCAv/CPP 100mmHg were calculated. The change from baseline (Δ) in MCAv was similar between the sexes during the GXT (p = .091, ωp2 = 0.05). However, ΔCPP (p < .001, ωp2 = 0.25) was greater in males at intensities ≥ 80% Wmax and ΔCVCi (p = .005, ωp2 = 0.15) was greater in females at 100% Wmax . Δ End-tidal CO2 (ΔEtCO2 ) was not different between the sexes during exercise (p = .606, ωp2 = -0.03). These data suggest there are sex-specific differences in cerebrovascular control, and these differences may only be identifiable at high and severe intensity exercise.
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Circulación Cerebrovascular , Prueba de Esfuerzo/normas , Entrenamiento de Intervalos de Alta Intensidad/métodos , Adulto , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Entrenamiento de Intervalos de Alta Intensidad/normas , Humanos , Masculino , Factores SexualesRESUMEN
Military performance depends on high-level cognition, specifically executive function (EF), while simultaneously performing strenuous exercise. However, most studies examine cognitive performance following, not during, exercise. Therefore, our aim was to examine the relationship between EF and exercise intensity. Following familiarization, 13 Reserve Officers' Training Corp cadets (age = 19.6 ± 2 yr, five women) completed a graded exercise test (GxT) and two executive function exercise tests (EFETs) separated by a duration of ≥24 h. The EFET was a combined iPad-based EF test (Cedar Operator Workload Assessment Tool) and GxT. Heart rate (HR) and prefrontal cortex (PFC) oxygenation [near-infrared spectroscopy (NIRS)] were continuously recorded. The EF score was analyzed for accuracy of responses (%hit rate). Heart rate reserve was calculated to normalize exercise intensity (%HRR). For PFC oxygenation recordings, NIRS variables were used to calculate the tissue saturation index (%TSI). Data from EFET trials were averaged into a singular response. The %hit rate declined at heart rate reserves (HRRs) of ≥80%, reaching nadir at 100% HRR (74.09 ± 10.63%, P < 0.01). The tissue saturation index (TSI) followed a similar pattern, declining at ≥70% of HRR and at a greater rate during EFET compared with during GxT (P < 0.01), reaching a nadir in both conditions at 100% HRR (60.39 ± 2.94 vs. 63.13 ± 3.16%, P < 0.01). Therefore, EF decline is dependent on exercise intensity, as is %TSI. These data suggest that reductions in EF during high-intensity exercise are at least in part related to attenuated PFC oxygenation. Thus, interventions that improve PFC oxygenation may improve combined exercise and EF performance.NEW & NOTEWORTHY The executive functioning aspect of cognition was evaluated during graded exercise in Reserve Officers' Training Corps cadets. Executive function declined at exercise intensities of ≥80% of heart rate reserve. The decline in executive function was coupled with declines in the oxygenation of the prefrontal cortex, the brain region responsible for executive functioning. These data define the executive function-exercise intensity relationship and provide evidence supporting the reticular activation hypofrontality theory as a model of cognitive change.
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Función Ejecutiva , Ejercicio Físico , Adolescente , Adulto , Cognición , Prueba de Esfuerzo , Femenino , Humanos , Corteza Prefrontal , Adulto JovenRESUMEN
To examine the effects of caffeine during exercise in fire protective ensemble (FPE), 10 healthy males completed 3 x 10 min bouts of treadmill exercise on two separate days. Sixty minutes prior to exercise either 6 mg/kg of caffeine (CAFF) or dextrose placebo (PLA) capsules were ingested (randomly assigned, double blind). End-exercise gastrointestinal temperature (T(gi)) was higher in CAFF compared to PLA (38.80 +/- 0.08 degrees C vs. 38.43 +/- 0.11 degrees C, p < or = 0.01). Ventilation (V(E)) and tidal volume (V(t)) were also significantly higher in CAFF, which resulted in higher consumption of air from the self-contained breathing apparatus. While perceived exertion in the caffeine condition was decreased (p < or = 0.05) compared to placebo, the higher T(gi) values increased calculated physiological strain index in CAFF (p < or = 0.01). Caffeine appears to alter the physiological and psycho-physical responses to exercise in FPE and may influence factors related to work tolerance in firefighting. These findings are relevant to occupations such as firefighting where workers are encapsulated during exposure to heavy physical work and/or environmental heat. The results indicate that workers may be more susceptible to heat-related fatigue, illness or injury with ingestion of significant amounts of caffeine. To the authors' knowledge this is the first study involving humans and exercise to detect an increase in body temperature with caffeine ingestion.
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Cafeína/metabolismo , Ejercicio Físico/fisiología , Incendios , Ventiladores Mecánicos , Adulto , Cafeína/administración & dosificación , Ergonomía , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
With age, cerebrovascular and neurodegenerative diseases (e.g., dementia and Alzheimer's) are some of the leading causes of death in the United States. Related to these outcomes is the increased prevalence of hypertension, which independently increases the development of cerebrovascular and neurodegenerative diseases. While a direct mechanistic link between hypertension and poor brain health is unknown, many hypothesize that the etiology stems from poor blood pressure (BP) and cerebrovascular regulation. This dysfunction fosters hypoperfusion of the brain, causing stress to the tissue through a nutrient mismatch, subtly damaging the brain over many years. Current Western medical treatment relies on pharmacological treatment (mainly beta-blockers, angiotensin-converting enzyme inhibitors, or a combination of the two). However, Western treatments have not been successful in mitigating brain health outcomes and are burdened with unwanted side effects and non-adherence issues. Alternatively, traditional East Asia medicine has used acupuncture as a treatment for hypertension and may offer a promising approach in response to the limitations of conventional therapy. While detailed clinical and mechanistic experimental evidence is lacking, acupuncture has been observed to reduce BP and improve endothelial function in hypertensive adults. Further, acupuncture has been shown to have specific cerebrovascular effects, increasing cerebrovascular reactivity in healthy adults, highlighting possible neuroprotective properties. Therefore, our review is aimed at evaluating acupuncture as a treatment for hypertension and the potential impact on brain health. We will interrogate the current literature as well as discuss the proposed neural and vascular mechanisms by which acupuncture acts.