The Influence of Heat Shock Protein 90 on Sweating and Cutaneous Vasodilation in Older Adults Exercising in the Heat

Heat Shock Protein 90 (HSP90) is involved in numerous cellular enzymatic processes and it is up‐regulated during exercise in the heat in a variety of cell types. In vitro and in vivo evidence indicates that HSP90 directly enhances nitric oxide (NO) bioavailability via binding to and stabilization of NO synthase. In young males, we previously demonstrated a role for HSP90 in mediating cutaneous vasodilation, but not sweating, during exercise in the heat and this effect was determined to be NO‐dependent. Healthy ageing attenuates both cutaneous vasodilation and sweating responses during exercise in the heat, in part, due to reduced NO bioavailability. However, the contribution of HSP90 in mediating these heat loss responses in older adults remains poorly understood. Thus, the purpose of this study was to evaluate the contribution of HSP90 in modulating sweating and cutaneous vasodilation in healthy habitually active older adults exercising in the heat and to determine whether this contribution acts through the NO pathway. Eleven (M=8; F=3) healthy older adults (55 ± 5 years) exercised for 50 min at 55% VO 2peak in the heat (35°C, 30% relative humidity). Cutaneous vascular conductance (CVC, measured via laser Doppler flowmetry) and sweating (measured via ventilated capsules) were measured at four forearm skin sites receiving either: 1) Lactated Ringer's solution (Control), 2) 10 mM N G ‐nitro‐L‐arginine methyl ester (L‐NAME, a specific NO synthase inhibitor), 3) 178 mM Geldanamycin (Gelda, an HSP90 inhibitor), or 4) a combination of 10 mM L‐NAME +178 mM Gelda (L+G), via intradermal microdialysis. A 5% DMSO solution was used to fully dissolve Gelda, and was also added to the other sites for consistency. At the end of exercise, CVC was not different between Gelda (68 ± 18% CVC max ) and Control (65 ± 12% CVC max ; all P < 0.05) sites. However, CVC was reduced at L‐NAME (52 ± 20% CVC max ) and L+G (52 ± 17% CVC max ) sites, relative to both Control and Gelda sites (all P<0.05). Sweat rates were lower at the end of exercise for Gelda (1.38 ± 0.89 mg/min/cm 2 ), L‐NAME (1.16 ± 0.69 mg/min/cm2) and L+G (1.37 ± 0.79 mg/min/cm2) sites, relative to Control (1.51 ± 0.93 mg/min/cm2) (all P<0.05). Furthermore, sweating was reduced at the L‐NAME site relative to both Gelda and L+G sites (both P<0.05). In summary, these results demonstrate that in healthy habitually active older adults exercising in the heat, HSP90 inhibition does not influence cutaneous vasodilation, despite a clear role for NO in this response. Conversely, HSP90 does attenuate the sweating response in this group. The underlying reasons for the differing effects of HSP90 inhibition on cutaneous vasodilation and sweating between younger and older adults require further investigation. Support or Funding Information Funding support: Canadian Institutes of Health Research (held by Dr. Kenny). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

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