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Introduction: To determine if electrolyte or carbohydrate supplementation vs. water would limit the magnitude of dehydration and decline in cognitive function in humans following long-duration hyperthermic-exercise., Methods: 24 subjects performed 3 visits of 2 h walking (3mph/7% grade) in an environmental chamber (33 °C/10% relative humidity). In random order, subjects consumed water (W), electrolytes (Gatorade Zero; E), or electrolytes+carbohydrates (Gatorade; E+C). Throughout exercise (EX), subjects carried a 23 kg pack and drank ad-libitum. Pre-and post-EX, body mass (BM) and plasma osmolality (pOsm) were measured. Physiological Strain Index (PSI) and core temperature (T C ) were recorded every 15 min. Plasma glucose (GLU) was measured every 30 min. Cognitive processing (SCWT) was measured post-EX and compared to baseline (BL). A subset of 8 subjects performed a normothermic (N) protocol (21 °C/ambient humidity) to ascertain how the exercise stimulus influenced hydration status and cognition without heat., Results: There were no significant differences between fluid conditions (W, E, E+C) for BM loss (Δ2.5 ± 0.2, 2.5 ± 0.2, 2.3 ± 0.2 kg), fluid consumption (1.9 ± 0.2, 1.9 ± 0.2, 1.8 ± 0.2L), pOsm (Δ1.5 ± 2.7, 2.2 ± 2.4, 2.0 ± 1.5 mmol/L), peak-PSI (7.5 ± 0.4, 7.0 ± 0.6, 7.9 ± 0.5), and peak-T C (38.7 ± 0.1, 38.6 ± 0.2, 38.8 ± 0.2 °C). GLU decreased significantly in W and E, whereas it increased above BL in E+C at 60, 90, and 120 min (P < 0.05). Compared to BL values (43.6 ± 26 ms), SCWT performance significantly decreased in all conditions (463 ± 93, 422 ± 83, 140 ± 52 ms, P < 0.05). Importantly, compared to W and E, the impairment in SCWT was significantly attenuated in E+C (P < 0.05). As expected, when compared to the heat-stress protocol (W, E, E+C), N resulted in lower BM loss, fluid consumption, and peak-PSI (1.1 ± 0.1 kg, 1.2 ± 0.7L, 4.8, respectively), and improved SCWT performance., Conclusions: These data are the first to suggest that, independent of supplementation variety, cognitive processing significantly decreases immediately following long-duration exercise in the heat in healthy humans. Compared to water and fluids supplemented with only electrolytes, fluids supplemented with carbohydrates significantly blunts this decrease in cognitive function., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The increase in interstitial potassium (K + ) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K + in exercise hyperemia, we perfused skeletal muscle with K + before contractions, such that the effect of any endogenously-released K + would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF) (Doppler ultrasound) and forearm vascular conductance (FVC) (FBF/mean arterial pressure) during 4 min of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions, 2) infusion of KCl before the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly before the onset of exercise (control: 39 ± 6 vs. KCl: 81 ± 12 and SNP: 82 ± 13 ml·min -1 ·100 mmHg -1 ; both P < 0.05 vs. control). Infusion of KCl at rest diminished the hyperemic (ΔFBF) and vasodilatory (ΔFVC) response to subsequent exercise by 22 ± 5% and 30 ± 5%, respectively (both P < 0.05 vs. control), whereas SNP did not affect the change in FBF ( P = 0.74 vs. control) or FVC ( P = 0.61 vs. control) from rest to steady-state exercise. These findings implicate the K + ion as an essential vasodilator substance contributing to exercise hyperemia in humans. NEW & NOTEWORTHY Our findings support a significant and obligatory role for potassium signaling in the local vasodilatory and hyperemic response to exercise in humans.

Dietary nitrate (NO3-) is converted to nitrite (NO2-) and can be further reduced to the vasodilator nitric oxide (NO) amid a low O 2 environment. Accordingly, dietary NO3- increases hind limb blood flow in rats during treadmill exercise; however, the evidence of such an effect in humans is unclear. We tested the hypothesis that acute dietary NO3- (via beetroot [BR] juice) increases forearm blood flow (FBF) via local vasodilation during handgrip exercise in young adults (n = 11; 25 ± 2 years). FBF (Doppler ultrasound) and blood pressure (Finapres) were measured at rest and during graded handgrip exercise at 5%, 15%, and 25% maximal voluntary contraction (MVC) lasting 4 min each. At the highest workload (25% MVC), systemic hypoxia (80% SaO 2 ) was induced and exercise continued for three additional minutes. Subjects ingested concentrated BR (12.6 mmol nitrate (n = 5) or 16.8 mmol nitrate (n = 6) and repeated the exercise bout either 2 (12.6 mmol) or 3 h (16.8 mmol) postconsumption. Compared to control, BR significantly increased FBF at 15% MVC (184 ± 15 vs. 164 ± 15 mL/min), 25% MVC (323 ± 27 vs. 286 ± 28 mL/min), and 25% + hypoxia (373 ± 39 vs. 343 ± 32 mL/min) and this was due to increases in vascular conductance (i.e., vasodilation). The effect of BR on hemodynamics was not different between the two doses of BR ingested. Forearm VO 2 was also elevated during exercise at 15% and 25% MVC. We conclude that acute increases in circulating NO3- and NO2- via BR increases muscle blood flow during moderate- to high-intensity handgrip exercise via local vasodilation. These findings may have important implications for aging and diseased populations that demonstrate impaired muscle perfusion and exercise intolerance., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Skeletal muscle haemodynamics and circulating adenosine triphosphate (ATP) responses during hypoxia and exercise are blunted in older (OA) vs. young (YA) adults, which may be associated with impaired red blood cell (RBC) ATP release. Rho‐kinase inhibition improves deoxygenation‐induced ATP release from OA isolated RBCs. We tested the hypothesis that Rho‐kinase inhibition (via fasudil) in vivo would improve local haemodynamic and ATP responses during hypoxia and exercise in OA. Healthy YA (25 ± 3 years; n = 12) and OA (65 ± 5 years; n = 13) participated in a randomized, double‐blind, placebo‐controlled, crossover study on two days (≥5 days between visits). A forearm deep venous catheter was used to administer saline/fasudil and sample venous plasma ATP ([ATP]V). Forearm vascular conductance (FVC) and [ATP]V were measured at rest, during isocapnic hypoxia (80% SpO2${S_{{\rm{p}}{{\rm{O}}_{\rm{2}}}}}$), and during graded rhythmic handgrip exercise that was similar between groups (5, 15 and 25% maximum voluntary contraction (MVC)). Isolated RBC ATP release was measured during normoxia/hypoxia. With saline, ΔFVC was lower (P < 0.05) in OA vs. YA during hypoxia (∼60%) and during 15 and 25% MVC (∼25–30%), and these impairments were abolished with fasudil. Similarly, [ATP]V and ATP effluent responses from normoxia to hypoxia and rest to 25% MVC were lower in OA vs. YA and improved with fasudil (P < 0.05). Isolated RBC ATP release during hypoxia was impaired in OA vs. YA (∼75%; P < 0.05), which tended to improve with fasudil in OA (P = 0.082). These data suggest Rho‐kinase inhibition improves haemodynamic responses to hypoxia and moderate intensity exercise in OA, which may be due in part to improved circulating ATP. Key points: Skeletal muscle blood flow responses to hypoxia and exercise are impaired with age. Blunted increases in circulating ATP, a vasodilator, in older adults may contribute to age‐related impairments in haemodynamics.Red blood cells (RBCs) are a primary source of circulating ATP, and treating isolated RBCs with a Rho‐kinase inhibitor improves age‐related impairments in deoxygenation‐induced RBC ATP release.In this study, treating healthy older adults systemically with the Rho‐kinase inhibitor fasudil improved blood flow and circulating ATP responses during hypoxia and moderate intensity handgrip exercise compared to young adults, and also tended to improve isolated RBC ATP release.Improved blood flow regulation with fasudil was also associated with increased skeletal muscle oxygen delivery during hypoxia and exercise in older adults.This is the first study to demonstrate that Rho‐kinase inhibition can significantly improve age‐related impairments in haemodynamic and circulating ATP responses to physiological stimuli, which may have therapeutic implications. [ABSTRACT FROM AUTHOR]

Human aging is associated with reduced skeletal muscle perfusion during exercise, which may be a result of impaired endothelium-dependent dilation and/or attenuated ability to blunt sympathetically mediated vasoconstriction. Intra-arterial infusion of ascorbic acid (AA) increases nitric oxide-mediated vasodilation and forearm blood flow (FBF) during handgrip exercise in older adults, yet it remains unknown whether an acute oral dose can similarly improve FBF or enhance the ability to blunt sympathetic vasoconstriction during exercise. We hypothesized that 1) acute oral AA would improve FBF (Doppler ultrasound) and oxygen consumption (VO2) via local vasodilation during graded rhythmic handgrip exercise in older adults (protocol 1), and 2) AA ingestion would not enhance sympatholysis in older adults during handgrip exercise (protocol 2). In protocol 1 (n = 8; 65 ± 3 yr), AA did not influence FBF or VO2 during rest or 5% maximal voluntary contraction (MVC) exercise, but increased FBF (199 ± 13 vs. 248 ± 16 ml/min and 343 ± 24 vs. 403 ± 33 ml/min; P < 0.05) and VO2 (26 ± 2 vs. 34 ± 3 ml/min and 43 ± 4 vs. 50 ± 5 ml/min; P < 0.05) at both 15 and 25% MVC, respectively. The increased FBF was due to elevations in forearm vascular conductance (FVC). In protocol 2 (n = 10; 63 ± 2 yr), following AA, FBF was similarly elevated during 15% MVC (~20%); however, vasoconstriction to reflex increases in sympathetic activity during -40 mmHg lower-body negative pressure at rest (ΔFVC: -16 ± 3 vs. -16 ± 2%) or during 15% MVC (ΔFVC: -12 ± 2 vs. -11 ± 4%) was unchanged. Our collective results indicate that acute oral ingestion of AA improves muscle blood flow and VO2 during exercise in older adults via local vasodilation. [ABSTRACT FROM AUTHOR]

PURPOSE: To determine if electrolyte or carbohydrate supplementation vs. plain water would limit the magnitude of dehydration and decline in cognitive function in humans. METHODS: 24 subjects performed 3 visits consisting of 2hrs of walking at 3mph/7% grade in an environmental chamber set to 33ºC/10% RH. In random order, subjects consumed water (W), water+electrolyte (GZ), or water+electrolyte+sugar (G). Throughout exercise (EX), subjects carried a 23kg pack, and drank ad libitum. Pre and post EX, body mass (BM) and plasma osmolality (pOsm) were measured. Physiological Strain Index (PSI), an index of cardiovascular and thermal stress, and core temperature (TC) were recorded every 15mins. Plasma glucose (GLU) was measured every 30mins. Cognitive processing speed, measured via the Stroop Test (SCWT), was measured post EX and compared to baseline (BL). A subset of 8 subjects performed a normothermic (N) protocol (21ºC/ambient humidity) to ascertain how the exercise stimulus would influence hydration status and cognitive function in the absence of heat. RESULTS: There were no significant differences between fluid conditions (W, GZ, & G) for BM loss (Δ3.2±0.2, 3.1±0.2, & 3.0±0.3kg), fluid consumption (1.9±0.2, 1.9±0.2, & 1.8±0.2L), pOsm (Δ1.5±2.7, 2.2±2.4, & 2.0±1.5mmol/L), peak PSI (7.5±0.4, 7.0±0.6, & 7.9±0.5), and peak TC (38.7±0.1, 38.6±0.1, & 38.8±0.2ºC). Compared to W and GZ, GLU significantly increased from BL in the G condition (107±4 & 109±3mg/dL at 90 & 120mins, P<0.05). Compared to BL values, SCWT performance significantly decreased in all conditions (463±93, 422±83, & 140±52ms for W, GZ, & G, P<0.05). Importantly, compared to the W and GZ conditions, the SCWT performance was significantly attenuated in the G condition (P<0.05). As expected, when compared to the heat stress protocol (W, GZ, & G), the N condition resulted in lower BM loss, fluid consumption, and peak PSI (2.0±0.1kg, 1.2±0.7L, & 4.8, respectively). CONCLUSIONS: These data are the first to suggest that, independent of supplementation variety, cognitive processing significantly decreases immediately following long duration exercise in the heat in healthy humans. Compared to water and fluids supplemented with only electrolytes, fluids supplemented with carbohydrates significantly blunts this decrease in cognitive function. [ABSTRACT FROM AUTHOR]