Superoxide and NADPH oxidase do not modulate skin blood flow in older exercising adults with and without type 2 diabetes.

OBJECTIVE: High aerobic fitness may prevent age-related decrements in cutaneous vasodilation while type 2 diabetes may exacerbate this decline. The mechanisms underlying these responses remain unclear, but may be due to an excess of reactive oxygen species. We hypothesized that superoxide scavenging or NADPH oxidase inhibition would improve cutaneous vasodilation in older adults exercising in the heat, particularly in healthy low-fit individuals and those with type 2 diabetes. METHODS: Twenty seven older adults were evenly separated into three groups (healthy low-fit: VO2peak = 24.4 ±â€¯2.4 ml·kg-1·min-1, 61 ±â€¯8 years; healthy high-fit: 42.5 ±â€¯9.7 ml·kg-1·min-1, 56 ±â€¯6 years; type 2 diabetes: 30.0 ±â€¯7.6, ml·kg-1·min-1, 58 ±â€¯7 years). The healthy low-fit and type 2 diabetes groups performed two successive 30-min cycling bouts at 65%VO2peak in the heat (35°C), separated by 30-min rest. The high-fit group cycled at the same absolute heat load (and therefore requirement for heat loss) as their healthy low-fit counterparts during the first exercise bout (Ex1) and at the same relative intensity (65%VO2peak) during the second (Ex2). Forearm cutaneous vascular conductance (CVC%max) was measured at microdialysis sites perfused with: 1) lactated Ringer's solution (control); 2) 10 mM NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor); 3) 100 µM apocynin (NADPH oxidase inhibitor); 4) 10 µM tempol (superoxide dismutase mimetic), with responses compared at baseline, end-Ex1, and end-Ex2. RESULTS: In all groups, L-NAME consistently reduced CVC%max relative to the other treatment sites by ~16-21% during Ex1 and by ~22-27% during Ex2 (all P < 0.05). Conversely, superoxide scavenging and NADPH oxidase inhibition did not influence CVC%max (all P > 0.05). CONCLUSION: Superoxide and NADPH oxidase do not modulate cutaneous vasodilation in healthy low- or high-fit older adults exercising in the heat, regardless of aerobic fitness level or relative exercise intensity employed, nor do they influence cutaneous vasodilation during an exercise-heat stress in those with type 2 diabetes. However, NOS remains an important modulator of cutaneous vasodilation during exercise in all groups.

Exogenous Activation of Protease-Activated Receptor 2 Attenuates Cutaneous Vasodilatation and Sweating in Older Men Exercising in the Heat.

BACKGROUND: Protease-activated receptor 2 (PAR2) exists in the cutaneous vasculature and eccrine sweat glands. We previously showed that in young habitually active men, exogenous PAR2 activation via the agonist SLIGKV-NH2 had no effect on heat loss responses of cutaneous vasodilatation and sweating during rest or exercise in the heat. However, ageing is associated with altered mechanisms governing these responses. Thus, the effect of exogenous PAR2 activation on cutaneous vasodilatation and sweating in older individuals may differ from that in young adults. METHODS: Local cutaneous vascular conductance (CVC) and sweat rate were measured in 9 older males (62 ± 4 years) at four forearm skin sites treated with the following: (1) lactated Ringer solution (control), (2) 0.05 mM, (3) 0.5 mM, or (4) 5 mM SLIGKV-NH2. Measurements were performed while participants rested in a non-heat-stress environment (25°C) for ∼60 min and an additional 50 min thereafter in the heat (40°C). Participants then performed 50 min of cycling at a fixed metabolic heat load of 200 W/m2 (to maintain the same thermal drive for heat loss between participants) followed by a 30-min recovery. RESULTS: CVC during non-heat-stress resting was elevated from the control site with 5 mM SLIGKV-NH2 (p ≤ 0.05), but this response was not observed during ambient heat exposure. By contrast, 5 mM SLIGKV-NH2 lowered CVC during the early stage (10 and 20 min) of exercise compared to the control site (all p ≤ 0.05). Although sweating during non-heat-stressed and heat-stressed resting was not affected by any dose of SLIGKV-NH2, it was reduced with all SLIGKV-NH2 doses relative to the control site during and following exercise (all p ≤ 0.05). CONCLUSION: We show that while exogenous PAR2 activation induces cutaneous vasodilatation at rest under non-heat-stressed conditions, it attenuates cutaneous vasodilatation and sweating during and following an exercise-induced heat stress in older men.

Heat shock protein 90 does not contribute to cutaneous vasodilatation in older adults during heat stress.

OBJECTIVES: Heat shock protein 90 (HSP90) contributes to cutaneous vasodilatation during exercise in the heat through nitric oxide (NO) synthase (NOS)-dependent mechanisms in young adults. We hypothesized that similar responses would be observed in older middle-aged adults. METHODS: In nineteen habitually active older middle-aged (56 ± 5 years) men (n = 9) and women (n = 10), cutaneous vascular conductance (CVC) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (Control), (b) 10 mmol/L L-NAME (NOS inhibitor), (c) 178 µmol/L geldanamycin (HSP90 inhibitor), or (d) 10 mmol/L L-NAME and 178 µmol/L geldanamycin combined. Participants rested in an upright semi-recumbent position in the heat (35°C) for 70 minutes, followed by a 50-minute bout of moderate-intensity cycling (~55% peak oxygen uptake) and a 30-minute recovery period in the heat. RESULTS: In both men and women, we observed no significant effects of HSP90 inhibition on CVC throughout rest, exercise, and recovery in the heat (all P > 0.27). Conversely, NOS inhibition and dual NOS and HSP90 inhibition attenuated CVC relative to Control throughout the protocol (all P ≤ 0.05). CONCLUSIONS: While NOS mediates cutaneous vasodilatation during rest, exercise, and recovery in the heat, HSP90 does not measurably influence this response in habitually active older middle-aged men or women under these conditions.