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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]

To determine whether carbohydrate ingestion would reduce cognitive dysfunction in humans following long duration passive heat stress (PHS) versus consuming electrolytes alone. Fifteen young (27 ± 4 y) healthy adults were exposed to 120 min of PHS through the use of a liquid perfused suit (50 °C) on two randomized visits. Subjects consumed fluids supplemented with electrolytes (E) or electrolytes + carbohydrates (E + C). Pre- and post-heat stress, body mass (BM) and plasma osmolality (pOsm) were measured. Heart rate (HR), blood pressure (BP), Physiological Strain Index (PSI), core temperature (T c), plasma glucose, respiration rate (RR), end-tidal CO2 (PetCO 2) and internal carotid artery (ICA) blood flow were recorded at baseline and every 15 min of heat stress. Cognitive function was assessed via the Automated Neuropsychological Assessment Metric at baseline and at 30- and 120 min during heat stress. There were no significant differences between fluid conditions for BM, pOsm, PSI, T c , RR or PetCO 2. Plasma glucose was ∼75% greater in the E + C condition compared to the E condition after 90 min of PHS (P < 0.05). Cognitive function (120 min) was impaired following PHS only in E condition (P < 0.05) and performance on complex cognitive tasks were better by ∼22–340% in the E + C vs. E (P < 0.05). Compared to the E condition, HR and BP were lower and ICA blood flow, vascular conductance, and glucose delivery was ∼90% greater in the E + C after 90 min of PHS (P < 0.05). These data are the first to demonstrate that carbohydrate ingestion may have a protective effect on cognitive function during long duration PHS. Furthermore, this protection was associated with preserved ICA blood flow and glucose delivery to the brain. The primary new findings of the present investigation are as follows: • Prolonged passive heat stress significantly impaired cognitive function as assessed by complex processing tasks. • Exogenous carbohydrate ingestion completely abolished the heat stress-induced impairment in cognitive function. • Exogenous carbohydrate ingestion attenuated the decline in global cerebral blood flow, and thus cerebral glucose delivery was significantly elevated during the bout of prolonged passive heat stress. • Heart rate and mean arterial pressure were lower during heat stress when carbohydrate was ingested, and thus the preserved cerebral blood flow was attributed to an elevated vascular conductance. [ABSTRACT FROM AUTHOR]