The effect of acute intradermal administration of ascorbate on heat loss responses in older adults with uncomplicated controlled hypertension.

NEW FINDINGS: What is the central question of this study? Does acute intradermal administration of the antioxidant ascorbate augment local forearm cutaneous vasodilatation and sweating via nitric oxide synthase (NOS)-dependent mechanisms during exercise-heat stress in older adults with uncomplicated controlled hypertension? What is the main finding and its importance? Relative to the control site, ascorbate had no effect on forearm cutaneous vascular conductance (CVC) and sweat rate, although CVC was reduced with NOS inhibition in older adults with hypertension. Acute local administration of ascorbate to forearm skin does not modulate heat loss responses during exercise-heat stress in older adults with hypertension. ABSTRACT: Nitric oxide synthase (NOS) contributes to the heat loss responses of cutaneous vasodilatation and sweating during exercise. However, the contribution of NOS may be attenuated in individuals with uncomplicated, controlled hypertension due to elevated oxidative stress, which can reduce NO bioavailability. We evaluated the hypothesis that the acute local intradermal administration of the antioxidant ascorbate would enhance cutaneous vasodilatation and sweating via NOS-dependent mechanisms during an exercise-heat stress in adults with hypertension. Habitually active adults who were normotensive (n = 14, 7 females, 62 ± 4 years) or had uncomplicated, controlled hypertension (n = 13, 6 females, 62 ± 5 years) performed 30 min of moderate-intensity (50% of their pre-determined peak oxygen uptake) semi-recumbent cycling in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and sweat rate were assessed at four forearm skin sites continuously perfused with (1) lactated Ringer solution (Control), (2) 10 mM antioxidant ascorbate, (3) 10 mM NG -nitro-l-arginine methyl ester (l-NAME), a non-selective NOS inhibitor, or (4) a combination of ascorbate and l-NAME. Relative to Control, no effect of ascorbate was observed on CVC or sweating in either group (P = 0.619). However, l-NAME reduced CVC relative to Control in both groups (P ≤ 0.038). No effect of any treatment on sweating was observed (P ≥ 0.306). Thus, acute local administration of ascorbate to forearm skin does not enhance the activation of heat loss responses of cutaneous vasodilatation and sweating in older adults, and those with hypertension during an exercise-heat stress.

Revisiting regional variation in the age-related reduction in sweat rate during passive heat stress.

Aging is associated with attenuated sweat gland function, which has been suggested to occur in a peripheral-to-central manner. However, evidence supporting this hypothesis remains equivocal. We revisited this hypothesis by evaluating the sweat rate across the limbs and trunk in young and older men during whole-body, passive heating. A water-perfused suit was used to raise and clamp esophageal temperature at 0.6°C (low-heat strain) and 1.2°C (moderate-heat strain) above baseline in 14 young (24 (SD 5) years) and 15 older (69 (4) years) men. Sweat rate was measured at multiple sites on the trunk (chest, abdomen) and limbs (biceps, forearm, quadriceps, calf) using ventilated capsules (3.8 cm2 ). Sweat rates, expressed as the average of 5 min of stable sweating at low- and moderate-heat strain, were compared between groups (young, older) and regions (trunk, limbs) within each level of heat strain using a linear mixed-effects model with nested intercepts (sites nested within region nested within participant). At low-heat strain, the age-related reduction in sweat rate (older-young values) was greater at the trunk (0.65 mg/cm2 /min [95% CI 0.44, 0.86]) compared to the limbs (0.42 mg/cm2 /min [0.22, 0.62]; interaction: p = 0.010). At moderate-heat strain, sweat rate was lower in older compared to young (main effect: p = 0.025), albeit that reduction did not differ between regions (interaction: p = 0.888). We conclude that, contrary to previous suggestions, the age-related decline in sweat rate was greater at the trunk compared to the limbs at low-heat strain, with no evidence of regional variation in that age-related decline at moderate-heat strain.

Effect of extracellular hyperosmolality on sweat rate during metaboreflex activation in passively heated young men.

Metaboreflex activation augments sweating during mild-to-moderate hyperthermia in euhydrated (isosmotic isovolemic) individuals. Recent work indicates that extracellular hyperosmolality may augment metaboreflex-mediated elevations in sympathetic nervous activity. Our primary objective was, therefore, to test the hypothesis that extracellular hyperosmolality would exacerbate metaboreflex-mediated increases in sweat rate. On two separate occasions, 12 young men [means (SD): 25 (5) yr] received a 90-min intravenous infusion of either 0.9% saline (isosmotic condition, ISO) or 3.0% saline (hyperosmotic condition, HYP), resulting in a postinfusion serum osmolality of 290 (3) and 301 (7) mosmol/kgH2O, respectively. A whole body water perfusion suit was then used to increase esophageal temperature by 0.8°C above resting. Participants then performed a metaboreflex activation protocol consisting of 90-s isometric handgrip exercise (40% of their predetermined maximum voluntary contraction), followed by 150 s of brachial occlusion (trapping produced metabolites within the limb). Metaboreflex-induced sweating was quantified as the change in global sweat rate (from preisometric handgrip exercise to brachial occlusion), estimated as the surface area-weighted average of local sweat rate on the abdomen, axilla, chest, bicep, quadriceps, and calf, measured using ventilated capsules (3.8 cm2). We also explored whether this response differed between body regions. The change in global sweat rate due to metaboreflex activation was significantly greater in HYP compared with ISO (0.03 mg/min/cm2 [95% confidence interval: 0.00, 0.06]; P = 0.047), but was not modulated by body region (site × condition interaction: P = 0.679). These findings indicate that extracellular hyperosmolality augments metaboreflex-induced increases in global sweat rate, with no evidence for region-specific differences.

Myths and methodologies: Reliability of forearm cutaneous vasodilatation measured using laser-Doppler flowmetry during whole-body passive heating.

Laser-Doppler flowmetry (LDF) is commonly used to assess cutaneous vasodilatation responses, but its reliability (i.e. consistency) during whole-body passive heating is unknown. We therefore assessed the reliability of LDF-derived indices of cutaneous vasodilatation during incremental whole-body heating. Fourteen young men (age: 24 (SD 5) years) completed three identical trials, each separated by 1 week. During each trial, a water-perfused suit was used to raise and clamp oesophageal temperature at 0.6°C (low-heat strain; LHS) and 1.2°C (moderate-heat strain; MHS) above baseline. LDF-derived skin blood flow (SkBF) was measured at three dorsal mid-forearm sites, with local skin temperature clamped at 34°C. Data were expressed as absolute cutaneous vascular conductance (CVCabs ; SkBF/mean arterial pressure) and normalised to maximal conductance (%CVCmax ) achieved via simultaneous local skin heating to 44°C and increasing oesophageal temperature to 1.8°C above baseline. Between-day reliability was characterised as measurement consistency across trials, while within-day reliability was characterised as measurement consistency across adjacent skin sites during each trial. Between- and within-day absolute reliability (coefficient of variation) generally improved with increasing heat strain, changing from poor (>25%) at baseline, poor-to-moderate (15-34%) at LHS, and moderate (10-25%) at MHS. Generally, these estimates were more consistent when expressed as %CVCmax . Conversely, relative reliability was mostly acceptable (intraclass correlation coefficient ≥0.70) during LHS and when data were expressed as CVCabs . These findings indicate that the consistency of LDF-derived CVC estimates during heat stress depends on the level of heat strain and method of data expression, which should be considered when designing and interpreting experiments.

Regional variation in the reliability of sweat rate measured via the ventilated capsule technique during passive heating.

The ventilated capsule technique is widely used to measure time-dependent changes in sweating in humans. However, evaluations of its reliability (consistency) have been restricted to the forearm, despite extensive regional heterogeneity in the sweating response. Given the importance of such information for experimental design, statistical analysis and interpretation, we determined the reliability of local sweat rate at nine sites during whole-body passive (resting) heating. On three separate occasions, a water-perfused suit was used to increase and clamp oesophageal temperature 0.6, 1.2 and 1.8°C above baseline in 14 young men [24 (SD 5) years of age], while sweat rate was measured at the forehead, chest, abdomen, biceps, forearm, hand, quadriceps, calf and foot using ventilated capsules (3.8 cm2 ). Absolute and relative reliability were determined via the coefficient of variation (CV) and intraclass correlation coefficient (ICC), respectively. At low heat strain (0.6°C), almost all sites had acceptable relative reliability (ICC ≥ 0.70) and moderate absolute reliability (CV < 25%). At moderate heat strain (1.2°C), only the abdomen, hand, quadriceps and foot had acceptable relative reliability, whereas the forehead, abdomen, forearm, hand and quadriceps had moderate absolute reliability. At high heat strain (1.8°C), relative reliability was acceptable at the abdomen, quadriceps, calf and foot, whereas the chest, abdomen, forearm, hand, quadriceps, calf and foot had moderate absolute reliability. Our findings indicate that the measurement site and level of heat strain impact the consistency of local sweat rate measured via the ventilated capsule technique, and we demonstrate the possible implications for research design and data interpretation.

Heat shock protein 90 modulates cutaneous vasodilation during an exercise-heat stress, but not during passive whole-body heating in young women.

Heat shock protein 90 (HSP90) modulates exercise-induced cutaneous vasodilation in young men via nitric oxide synthase (NOS), but only when core temperature is elevated ~1.0°C. While less is known about modulation of this heat loss response in women during exercise, sex differences may exist. Further, the mechanisms regulating cutaneous vasodilation can differ between exercise- and passive-heat stress. Therefore, in 11 young women (23 ± 3 years), we evaluated whether HSP90 contributes to NOS-dependent cutaneous vasodilation during exercise (Protocol 1) and passive heating (Protocol 2) and directly compared responses between end-exercise and a matched core temperature elevation during passive heating. Cutaneous vascular conductance (CVC%max ) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (control), (b) 178 µM Geldanamycin (HSP90 inhibitor), (c) 10 mM L-NAME (NOS inhibitor), or (d) combined 178 µM Geldanamycin and 10 mM L-NAME. Participants completed both protocols during the early follicular (low hormone) phase of the menstrual cycle (0-7 days). Protocol 1: participants rested in the heat (35°C) for 70 min and then performed 50 min of moderate-intensity cycling (~55% VO2peak ) followed by 30 min of recovery. Protocol 2: participants were passively heated to increase rectal temperature by 1.0°C, comparable to end-exercise. HSP90 inhibition attenuated CVC%max relative to control at end-exercise (p < .05), but not during passive heating. While NOS inhibition and combined HSP90 + NOS inhibition attenuated CVC%max relative to control for both protocols (all p < .05), they did not differ from each other. We show that HSP90 modulates cutaneous vasodilation NOS-dependently during exercise in young women, with no effect during passive heating, despite a similar NOS contribution.

Sex-differences in cholinergic, nicotinic, and ß-adrenergic cutaneous vasodilation: Roles of nitric oxide synthase, cyclooxygenase, and K+ channels.

Previous studies indicate that sex-related differences exist in the regulation of cutaneous vasodilation, however, the mechanisms remain unresolved. We assessed if sex-differences in young adults exist for cholinergic, nicotinic, and ß-adrenergic cutaneous vasodilation with a focus on nitric oxide synthase (NOS), cyclooxygenase (COX), and K+ channel mechanisms. In twelve young men and thirteen young women, four intradermal forearm skin sites were perfused with the following: 1) lactated Ringer's solution (control), 2) 10 mM Nω-nitro-l-arginine, a non-selective NOS inhibitor, 3) 10 mM ketorolac, a non-selective COX inhibitor, or 4) 50 mM BaCl2, a nonspecific K+ channel blocker. At all four sites, cutaneous vasodilation was induced by 1) 10 mM nicotine, a nicotinic receptor agonist, 2) 100 µM isoproterenol, a nonselective ß-adrenergic receptor agonist, and 3) 2 mM and 2000 mM acetylcholine, an acetylcholine receptor agonist. Nicotine and isoproterenol were administered for 3 min, whereas each acetylcholine dose was administered for 25 min. Regardless of treatment site, cutaneous vasodilation in response to nicotine and a high dose of acetylcholine (2000 mM) were lower in women than men. By contrast, isoproterenol induced cutaneous vasodilation was greater in women vs. men. Irrespective of sex, NOS inhibition or K+ channel blockade attenuated isoproterenol-mediated cutaneous vasodilation, whereas K+ channel blockade decreased nicotine-induced cutaneous vasodilation. Taken together, our findings indicate that while the mechanisms underlying cutaneous vasodilation are comparable between young men and women, sex-related differences in the magnitude of cutaneous vasodilation do exist and this response differs as a function of the receptor agonist.

Regional influence of nitric oxide on cutaneous vasodilatation and sweating during exercise-heat stress in young men.

NEW FINDINGS: What is the central question of this study? Do regional differences exist in nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and sweating during exercise-heat stress in young men. What is the main finding and its importance? Exercise-induced increases in cutaneous vasodilatation and sweating were greater on the chest and upper back compared to the forearm, although the NOS contribution to cutaneous vasodilatation was similar across all regions. Conversely, there was a greater NOS-dependent rate of change in sweating on the chest compared to the forearm, with a similar trend on the back. ABSTRACT: While it is established that nitric oxide synthase (NOS) is an important modulator of forearm cutaneous vasodilatation and sweating during an exercise-heat stress in young men, it remains unclear if regional differences exist in this response. In 15 habitually active young men (24 ± 4 (SD) years), cutaneous vascular conductance (CVC) and local sweat rate (LSR) were assessed at three body regions. On each of the dorsal forearm, chest and upper-back (trapezius), sites were continuously perfused with either (1) lactated Ringer solution (control) or (2) 10 Mm Nω -nitro-l-arginine (l-NNA, NOS inhibitor), via microdialysis. Participants rested in the heat (35°C) for ∼75 min, followed by 60 min of semi-recumbent cycling performed at a fixed rate of heat production of 200 W m-2 (equivalent to ∼42% V̇O2peak ). During exercise, the chest and upper-back regions showed higher CVC and LSR responses relative to the forearm (all P < 0.05). Within each region, l-NNA attenuated CVC and LSR relative to control (all P < 0.05). However, the NOS contribution was not different across regions for the rate of change and plateau for CVC or for the LSR plateau (all P > 0.05). Conversely, there was a greater NOS contribution to the rate of change for LSR at the chest relative to the forearm (P < 0.05) with a similar trend for the back. In habitually active young men, NOS-dependent cutaneous vasodilatation was similar across regions while the NOS contribution to LSR was greater on the chest relative to the forearm. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during an exercise-heat stress.

Contribution of nitric oxide synthase to cutaneous vasodilatation and sweating in men of black-African and Caucasian descent during exercise in the heat.

NEW FINDINGS: What is the central question of this study? Nitric oxide modulates cutaneous vasodilatation and sweating during exercise-induced heat stress in young men. However, it remains uncertain whether these effects are reduced in black-African descendants, who commonly demonstrate reduced nitric oxide bioavailability. Therefore, we assessed whether black-African descendants display reduced nitric oxide-dependent cutaneous vasodilatation and sweating compared with Caucasians in these conditions. What is the main finding and its importance? Nitric oxide-dependent cutaneous vasodilatation and sweating were similar between groups, indicating that reduced nitric oxide bioavailability in black-African descendants does not attenuate these heat-loss responses during an exercise-induced heat stress. ABSTRACT: Men of black-African descent are at an increased risk of heat-related illness relative to their Caucasian counterparts. This might be attributable, in part, to reduced cutaneous nitric oxide (NO) bioavailability in this population, which might alter local cutaneous vasodilatation and sweating. To evaluate this, we compared these heat-loss responses in young men (18-30 years of age) of black-African (n = 10) and Caucasian (n = 10) descent during rest, exercise and recovery in the heat. Participants were matched for physical characteristics and fitness, and they were all born and raised in the same temperate environment (i.e. Canada; second generation and higher). Both groups rested for 10 min and then performed 50 min of moderate-intensity exercise at 200 W m-2 , followed by 30 min of recovery in hot, dry heat (35°C, 20% relative humidity). Local cutaneous vascular conductance (CVC%max ) and sweat rate (SR) were measured at two forearm skin sites treated with either lactated Ringer solution (control) or 10 mm NG -nitro-l-arginine methyl ester (l-NAME, a nitric oxide (NO) synthase inhibitor). l-NAME significantly reduced CVC%max throughout rest, exercise and recovery in both groups (both P < 0.001). However, there were no significant main effects for the contribution of NO to CVC%max between groups (all P > 0.500). l-NAME significantly reduced local SR in both groups (both P < 0.050). The contribution of NO to SR was similar between groups such that l-NAME reduced SR relative to control at 40 and 50 min into exercise (both P < 0.05). We demonstrate that ethnicity per se does not influence NO-dependent cutaneous vasodilatation and sweating in healthy young men of black-African and Caucasian descent during exercise in dry heat.