No effect of ascorbate on cutaneous vasodilation and sweating in older men and those with type 2 diabetes exercising in the heat

Abstract

Aging and chronic disease such as type 2 diabetes (T2D) are associated with impairments in the body's ability to dissipate heat. To reduce the risk of heat‐related injuries in these heat vulnerable individuals, it is necessary to identify interventions that can attenuate this impairment. We evaluated the hypothesis that intradermal administration of ascorbate improves cutaneous vasodilation and sweating in older adults via nitric oxide synthase (NOS)‐dependent mechanisms during exercise in the heat and whether these improvements, if any, are greater in individuals with T2D. Older males with (n = 12, 61 ± 9 years) and without (n = 12, 64 ± 7 years) T2D performed two 30‐min bouts of cycling at a fixed rate of metabolic heat production of 500 W (~70% peak oxygen uptake) in the heat (35°C); each followed by a 20‐ and 40‐min recovery, respectively. Cutaneous vascular conductance (CVC) and sweat rate were measured at four intradermal microdialysis sites treated with either (1) lactated Ringer (Control), (2) 10 mmol/L ascorbate (an antioxidant), (3) 10 mmol/L L‐NAME (non‐selective NOS inhibitor), or (4) a combination of ascorbate + L‐NAME. In both groups, ascorbate did not modulate CVC or sweating during exercise relative to Control (all P > 0.05). In comparison to Control, L‐NAME alone or combined with ascorbate attenuated CVC during exercise (all P ≤ 0.05) but had no influence on sweating (all P > 0.05). We show that in both healthy and T2D older adults, intradermal administration of ascorbate does not improve cutaneous vasodilation and sweating during exercise in the heat. However, NOS plays an important role in mediating cutaneous vasodilation.

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 …”

“…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 .…”

Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating

“…Furthermore, T2D is a well‐established risk factor for cardiovascular disease (Gu, Cowie, & Harris, ) and is associated with endothelial dysfunction, as reflected by impaired Acetylcholine‐induced forearm vasodilatation (Mäkimattila et al., ; Woodman, Watts, Playford, Best, & Chan, ). In addition, T2D is associated with altered cutaneous vascular (microvascular) responses (Caballero et al., ; Colberg, Stansberry, McNitt, & Vinik, ; Sokolnicki, Roberts, Wilkins, Basu, & Charkoudian, ), although this is not always observed, especially when evaluated in relatively healthy individuals with well‐controlled T2D and free of co‐morbidities such as peripheral neuropathy (Fujii et al., ; Sokolnicki et al., ). To date, there remains a paucity of information on how, if at all, T2D might modulate the mechanisms regulating cutaneous blood flow.…”

Body Temperature Regulation During Exercise and Hyperthermia in Diabetics

“…The reduction in nitric oxide bioavailability in individuals with type 2 diabetes is well established [62,63,72,73] and may be further exacerbated by the presence of atherosclerotic plaques which are known to adversely alter endothelial function through interfering with nitric oxide signaling [74]. In fact, one study reported that the relative nitric oxide-dependent vasodilation during whole-body passive heating was similar between healthy controls and type 2 diabetics; however, absolute SkBF was lower in the latter group [72].…”