The Influence of Heat Shock Protein 90 on Sweating and Cutaneous Vasodilation in Young Males During Exercise in the Heat

The regulation of sweating and cutaneous vasodilation during exercise in the heat involves the integration of multiple pathways. Less understood however, is the potential influence of heat shock proteins on the regulation of these heat loss responses. Heat shock proteins have been shown to be elevated during exercise‐induced heat stress and may play a mediating role in the regulation of sweating and cutaneous vasodilation. Heat shock protein 90 (HSP90) in particular has been shown to modulate nitric oxide (NO) bioavailability in addition to its cellular activities, which in turn can influence sweating and cutaneous vascular responses. Thus, the purpose of this study was to elucidate the contribution of HSP90 in modulating sweating and cutaneous vasodilation during exercise in hot conditions and to determine whether this contribution acts through the NO pathway. Five young males (22 ± 1 years) exercised for 50 min at 55% VO 2max in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC, measured via laser Doppler flowmetry) and sweating (measured via ventilated capsules) were measured at four intradermal 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 inhibitor of NO synthase), 3) 178 mM Geldanamycin (Gelda, an inhibitor of HSP90), or 4) a combination of 178 mM Gelda + 10 mM L‐NAME (Combination, L+G). 5% DMSO was used in order to fully dissolve Gelda, and was subsequently added to all other sites to maintain consistency. In the first four subjects, CVC at the end of exercise was reduced at the LNAME (40 ± 11% CVC max ), Gelda (55 ± 10% CVC max ), and LNAME + Gelda (36 ± 5% CVC max ) sites relative to Control (67 ± 12% CVC max ; all P < 0.05). Moreover, the attenuation in CVC from Control at the Combination site (32 ± 2% CVC max ) was greater relative to when Gelda was perfused alone (12 ± 25% CVC max ; P=0.02), but similar to when L‐NAME was perfused alone (32 ± 6% CVC max ; P=0.51). In the fifth subject this trend was reversed in that relative to Control (68 ± 4% CVC max ), CVC at the end of the exercise bout was reduced only at the L‐NAME (38 ± 6% CVC max ; P=0.02), and L+G (36 ± 2% CVC max ; P=0.002) sites, with no significance at the Gelda site from Control (62 ± 10% CVC max ; P=0.42). With respect to sweating, we demonstrated that there was no effect of Gelda, L‐NAME, or the combination on sweating at the end of exercise (all P>0.1). In summary, our preliminary results demonstrate that HSP90 may play role in modulating cutaneous vasodilation during exercise in the heat; however, it remains to be determined the extent in which the NO pathway contributes to this role. Conversely, we show that HSP90 does not mediate local forearm sweating in young males during exercise in the heat. Support or Funding Information This study was supported by grants from the Natural Sciences and Engineering Research Council of Canada (Discovery grant, RGPIN‐06313‐2014 and Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014; funds held by Dr. Glen P. Kenny).

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