Local infusion of ascorbate augments NO‐dependent cutaneous vasodilatation during intense exercise in the heat

Abstract

Key pointsr Recent work demonstrates that nitric oxide (NO) contributes to cutaneous vasodilatation during moderate (400 W of metabolic heat production) but not high (700 W of metabolic heat production) intensity exercise bouts performed in the heat (35°C).r The present study evaluated whether the impairment in NO-dependent cutaneous vasodilatation was the result of a greater accumulation of reactive oxygen species during high (700 W of metabolic heat production) relative to moderate (500 W of metabolic heat production) intensity exercise.r It was shown that local infusion of ascorbate (an anti-oxidant) improves NO-dependent forearm cutaneous vasodilatation during high intensity exercise in the heat.r These findings provide novel insight into the physiological mechanisms governing cutaneous blood flow during exercise-induced heat stress and provide direction for future research exploring whether oxidative stress underlies the impairments in heat dissipation that may occur in older adults, as well as in individuals with pathophysiological conditions such as type 2 diabetes.Abstract Nitric oxide (NO)-dependent cutaneous vasodilatation is reportedly diminished during exercise performed at a high (700 W) relative to moderate (400 W) rate of metabolic heat production. The present study evaluated whether this impairment results from increased oxidative stress associated with an accumuluation of reactive oxygen species (ROS) during high intensity exercise. On two separate days, 11 young (mean ± SD, 24 ± 4 years) males cycled in the heat (35°C) at a moderate (500 W) or high (700 W) rate of metabolic heat production. Each session included two 30 min exercise bouts followed by 20 and 40 min of recovery, respectively. Cutaneous vascular conductance (CVC) was monitored at four forearm skin sites continuously perfused via intradermal microdialysis with: (1) lactated Ringer solution (Control); (2) 10 mM ascorbate (Ascorbate); (3) 10 mM L-NAME; or (4) 10 mM ascorbate + 10 mM L-NAME (Ascorbate + L-NAME). At the end of each 500 W exercise bout, CVC was attenuated with L-NAME (ß35% CVC max ) and Ascorbate + L-NAME (ß43% CVC max ) compared to Control (ß60% CVC max ; all P < 0.04); however, Ascorbate did not modulate CVC during exercise (ß60% CVC max ; both P > 0.87). Conversely, CVC was elevated with Ascorbate (ß72% CVC max ; both P < 0.03) but remained similar to Control (ß59% CVC max ) with L-NAME (ß50% CVC max ) and Ascorbate + L-NAME (ß47% CVC max ; all P > 0.05) at the end of both 700 W exercise bouts. We conclude that oxidative stress associated with an accumulation of ascorbate-sensitive ROS impairs NO-dependent cutaneous vasodilatation during intense exercise.

Thermoregulation in the Aging Population and Practical Strategies to Overcome a Warmer Tomorrow

“…Intriguingly, contemporary studies utilizing intradermal administration of ascorbate in both young and old adults exercising in the heat reported no significant elevations in CVC, as opposed to the earlier study by Holowatz and colleagues . This discrepancy was postulated to be contributed by the difference in T sk of the subjects during ascorbate administration in both studies.…”

“…In the latter study, passive heating of subjects, using a water‐perfused thermal suit could have prompted a comparatively greater rise in T sk as well as cutaneous oxidative stress . On the other hand, owing to the relatively moderate mean T sk achieved (≈35 °C) when subjects exercised in a hot and dry environment in the former study, resultant levels of oxidative stress could have been insufficient to induce significant alterations in cutaneous vascular response despite treatment with ascorbate . While evidence supporting this notion remains indirect, this association appears to be corroborated by an increase in oxidative marker, malondialdehyde (MDA), when young adults exercised under hot and humid ambient conditions as compared to temperate conditions …”

Oxidative stress does not influence local sweat rate during high‐intensity exercise

“…), we demonstrated an oxidative stress‐mediated reduction in NO‐dependent cutaneous vasodilatation during high (∼71% ) but not moderate‐intensity exercise (∼52% ) in the heat (35°C; Meade et al . ). However, it is still unknown whether the sweating response is affected in a similar way.…”

“…During the screening session, anthropometric data and were determined, the detailed procedures for which are reported elsewhere (Meade et al . ).…”

“…For examples of studies using cutaneous ascorbate administration (as well as l ‐NAME) via microdialysis, please see our previous report (Meade et al . ). Approximately 120 min was allowed between the placement of the microdialysis fibres and the start of baseline measurements to ensure that any local trauma associated with insertion of the needle and/or microdialysis fibre had subsided (Hodges et al .…”