Dietary nitrate supplementation increases nitrate and nitrite concentrations in human skin interstitial fluid.

Acute dietary nitrate (NO3-) supplementation can increase [NO3-], but not nitrite ([NO2-]), in human skeletal muscle, though its effect on [NO3-] and [NO2-] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO3--rich beetroot juice (BR; 9.6 mmol NO3-), and 6 young adults ingested 140 mL of a NO3--depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO3-] and [NO2-]. The relative recovery rate of NO3- and NO2- through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO3-] and [NO2-]. Baseline [NO3-] was lower, whereas baseline [NO2-] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO3-] and [NO2-] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 µM for Δ[NO3-] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO2-] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO2-] post BR ingestion was higher, whereas [NO3-] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO3- and NO2- distribution at rest and indicate that acute BR supplementation increases [NO3-] and [NO2-] in human skin interstitial fluid.

Ingestion of carbonated water increases middle cerebral artery blood velocity and improves mood states in resting humans exposed to ambient heat stress.

Sugar-free carbonated water is consumed worldwide. The consumption of carbonated water is high in summer, when the heat loss responses of sweating and skin vasodilation are activated, and thermal perceptions (thermal sensation and comfort) and mood states are negatively modulated. However, whether ingesting carbonated water under ambient heat exposure modulates cerebral blood flow index, heat loss responses, thermal perceptions, and mood states remains to be determined. In this study, 17 healthy, habitually active, young adults (eight women) ingested 4 °C noncarbonated or carbonated water under 37 °C ambient heat-stressed resting conditions. Both drinks increased the middle cerebral artery mean blood velocity, an index of cerebral blood flow, and mean arterial pressure, with carbonated water exhibiting higher elevations than noncarbonated water (P < 0.05). However, the heart rate, sweat rate, and skin blood flow during and after drinking remained unchanged between the two conditions (P > 0.05). The thermal sensation and comfort after drinking remained unchanged between the two conditions (P > 0.05); but, a drink-induced reduction in sleepiness was higher, and drink-induced elevations in motivation and exhilaration were higher after ingesting carbonated water than those after ingesting noncarbonated water (P < 0.05). The analyses suggest that in humans under ambient heat-stressed resting conditions, ingestion of cold carbonated water increases the cerebral blood flow index, blood pressure, motivation, and exhilaration, whereas it decreases sleepiness relative to ingestion of noncarbonated cold water. However, ingestion of cold carbonated water fails to modulate thermoregulatory responses and thermal perception as opposed to noncarbonated cold water.

New portable device for continuous measurement of sweat rate under heat stress during field tests.

We have developed a portable method to measure sweat rate (SR) under heat stress during field tests. We randomly divided 15 males and 17 females (23-78 yr) into a group, equation group (EG) to determine an equation to convert a unit of SR (mmHg) by the portable method to that (mg·min-1·cm-2) by the ventilation method, and another group, validation group (VG) to validate the equation. Since we repeated measurements twice in three subjects, we randomly assigned the two measurements to one of the two groups and analyzed the results in 18 and 17 subjects for EG and VG, respectively. Subjects cycled for 20 min at moderate intensity in a warm environment while chest SR was simultaneously measured with a capsule installed with 4.8 g of silica gel and two microfans (8.4 cm3 volume) and with another capsule (12.6 cm2 area) ventilated with dry air at 1.5 L·min-1. Since the esophageal temperature (Tes) threshold for increasing SR and the slope of SR at a given increase in Tes by the portable method (x) were in high agreement with those values obtained by the ventilation method (y) in both groups (all r > 0.88, P < 0.001), we determined regression equations for all subjects after pooling data from both groups: y = 1.11x - 3.99 and y = 1.05x + 0.01 when the 95% prediction limits were ±0.12°C and ±0.43 mg·min-1·cm-2·°C-1 with minimum mean differences over the range of 36.2°C-37.2°C and 0.2-2.4 mg·min-1·cm-2·°C-1, respectively, using Bland-Altman analysis. Based on these findings, we consider the portable device to be reliable enough to evaluate individual sweating capacity during field tests.NEW & NOTEWORTHY We developed a portable device to measure sweat rate continuously under heat stress during field tests, with precision similar to that obtained by the ventilation method, which has been used to evaluate individual sweat rate responses in laboratory tests. This new, portable device will provide more opportunities to determine factors influencing sweat rate in larger populations of subjects during field tests.

TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans.

ABSTRACT: Transient receptor potential ankyrin 1 (TRPA1) channel activation induces cutaneous vasodilation in humans in vivo. However, the mechanisms underlying this response remains equivocal. We hypothesized that nitric oxide synthase (NOS) and Ca2+ activated K+ (KCa) channels contribute to the TRPA1 channel-induced cutaneous vasodilation with no involvement of cyclooxygenase (COX). Cutaneous vascular conductance (CVC) in 9 healthy young adults was assessed at 4 dorsal forearm skin sites treated by intradermal microdialysis with (1) 1.985% dimethyl sulfoxide + 0.015% lactated Ringer solution with propylene glycol (vehicle control), (2) 10 mM l-NAME, a nonselective NOS inhibitor, (3) 10 mM ketorolac, a nonselective COX inhibitor, or (4) 50 mM tetraethylammonium, a nonselective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose-dependent manner (2.9%, 8.8%, 26%, and 80%, each lasting ≥30 minutes). Administration of ≥8.8% cinnamaldehyde increased CVC from baseline at the vehicle control site by as much as 27.4% (95% confidence interval of 5.3; P < 0.001). NOS inhibitor attenuated the cinnamaldehyde-induced increases in CVC at the 8.8%, 26%, and 80% concentrations relative to the vehicle control site (all P ≤ 0.05). In contrast, both the COX inhibitor and KCa channel blockers did not attenuate the cinnamaldehyde induced-increases in CVC relative to the vehicle control site for all concentrations (all P ≥ 0.130). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with no detectable contributions of COX and KCa channels.

Countdown before voluntary exercise induces muscle vasodilation with baroreflex-mediated decrease in muscle sympathetic nerve activity in humans.

We examined whether a countdown (CD) before voluntary cycling exercise induced prospective vascular adjustment for the exercise and, if so, whether and how muscle sympathetic nerve activity (MSNA) was involved in the responses. Young men performed voluntary cycling in a semirecumbent position (n = 14) while middle cerebral artery blood flow velocity (VMCA; Doppler ultrasonography), heart rate (HR), arterial pressure (AP; finger photoplethysmography), oxygen consumption rate (V̇o2), oxygen saturation in the thigh muscle (StO2; near-infrared spectrometry), cardiac output (CO; Modelflow method), and total peripheral resistance (TPR) were measured (experiment 1). Another group underwent the same exercise protocol but used only the right leg (n = 10) while MSNA (microneurography) was measured in the peroneal nerve of the left leg (experiment 2). All subjects performed eight trials with a ≥5-min rest between trials. In four trials randomly selected from the eight trials, exercise onset was signaled by a 30-s CD, whereas in the remaining four trials, exercise was started without CD. We found that CD first increased VMCA, HR, CO, and mean AP, and then decreased TPR and increased StO2 and V̇o2 (experiment 1; all P < 0.021). Furthermore, the CD-induced increase in mean AP decreased total MSNA and burst frequency (experiment 2; both P < 0.048) through the baroreflex, with decreased TPR and increased StO2 (experiment 2; both P < 0.001). The vasodilation and increased V̇o2 continued after the start of exercise. Thus CD before starting exercise induced the muscle vasodilatory response with a concomitant reduction in MSNA through the baroreflex to accelerate aerobic energy production after the start of exercise.NEW & NOTEWORTHY Prospective cardiovascular adjustment occurs before starting voluntary exercise, increasing heart rate and arterial pressure followed by muscle vasodilation; however, the precise mechanisms and significance for this vasodilation remain unknown. We found that during the countdown before starting exercise cerebral blood flow velocity increased, followed by increases in heart rate and arterial pressure, which suppressed MSNA through baroreflex, resulting in thigh muscle vasodilation to increase oxygen consumption rate, which might make it easier to start exercise.

Mathematical model to estimate the increase in firefighters' core temperature during firefighting activity with a portable calorimeter.

We developed a mathematical model to estimate the increase in firefighters' core body temperature from energy expenditure (EE) measured by accelerometry to prevent heat illness during firefighting. Wearing firefighter personal protective equipment, seven male subjects aged 23-42 years underwent a graded walking test on a treadmill while esophageal temperature (Tes) and skin temperature were measured with thermocouples and EE was measured with a tri-axial accelerometer. To estimate the increase in Tes from EE, we proposed a mathematical model composed of the heat capacity of active muscles (C1, kcal·°C-1), the heat capacity of the sum of resting muscles and skin (C2), the resistance to heat flux from C1 to C2 (R1, °C·min·kcal-1), and the resistance from C2 to the skin surface (R2). We determined the parameters while minimizing the differences between the estimated and measured changes in Tes profiles during graded walking. We found that C1 and C2 in individuals were highly correlated with their body weight (kg) and body surface area (m2), respectively, whereas R1 and R2 were similar across subjects. When the profiles of measured Tes (y) and estimated Tes (x) were pooled in all subjects, they were almost identical and were described by a regression equation without an intercept, y = 0.96x (r = 0.96, P < 0.0001), with a mean difference of - 0.01 ± 0.12 °C (mean ± SD) ranging from - 0.18 to 1.56 °C of the increase in Tes by Bland-Altman analysis. Thus, the model can be used for firefighters to prevent heat illness during firefighting.

Effects of hypervolemia by protein and glucose supplementation during aerobic training on thermal and arterial pressure regulations in hypertensive older men.

In Japan, the incidence of heat illness in older people has rapidly increased during midsummer in the last decade, and we suggested that whey-protein+carbohydrate supplementation during aerobic training would increased plasma volume (PV) to enhance thermoregulatory adaptation in older men (J Appl Physiol 107: 725-733, 2009); however, >60% of people age 65 and older suffer from hypertension, and the symptoms may be worsened by hypervolemia. To examine this, we randomly divided 21 older men (∼69 yr) with ∼160 mmHg for systolic and ∼90 mmHg for diastolic blood pressure at rest into two groups: Glc (n = 11) consuming glucose alone (25 g) and Pro-Glc (n = 10) consuming whey protein (10 g) + glucose (15 g), immediately after cycling exercise at 60-75% of peak aerobic capacity (V̇o2 peak) for 60 min/day, 3 days/wk, for 8 wk. Before and after training, we measured PV (dye dilution), baroreflex sensitivity (BRS) of heart rate (Valsalva maneuver), and carotid arterial compliance (CAC) from carotid arterial diameter (ultrasound imaging) responses to pulsatile arterial pressure change (photoplethysmography) at rest. Additionally, we measured esophageal temperature (Tes) and forearm skin blood flow (plethysmography) during exercise at 60% pretraining V̇o2 peak for 20 min in a warm environment. We found that the forearm skin vascular conductance response to increased Tes was enhanced in Pro-Glc with increased PV, but this was not found in Glc; however, despite the increased PV, arterial blood pressures rather decreased with increased CAC and BRS in Pro-Glc. Thus, the prescription was applicable to older men with hypertension to prevent heat illness during exercise.

Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women.

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0 °C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% (P < 0.001) and 11% (P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma (P < 0.001), although all remained unchanged in the CNT trial (P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial (P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% (P = 0.028), 102% (P = 0.027), and 69% (P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.