Heat shock protein 90 modulates cutaneous vasodilation during an exercise-heat stress, but not during passive whole-body heating in young women

Physiol Rep. 2020 Aug;8(16):e14552. doi: 10.14814/phy2.14552.


Heat shock protein 90 (HSP90) modulates exercise-induced cutaneous vasodilation in young men via nitric oxide synthase (NOS), but only when core temperature is elevated ~1.0°C. While less is known about modulation of this heat loss response in women during exercise, sex differences may exist. Further, the mechanisms regulating cutaneous vasodilation can differ between exercise- and passive-heat stress. Therefore, in 11 young women (23 ± 3 years), we evaluated whether HSP90 contributes to NOS-dependent cutaneous vasodilation during exercise (Protocol 1) and passive heating (Protocol 2) and directly compared responses between end-exercise and a matched core temperature elevation during passive heating. Cutaneous vascular conductance (CVC%max ) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (control), (b) 178 μM Geldanamycin (HSP90 inhibitor), (c) 10 mM L-NAME (NOS inhibitor), or (d) combined 178 μM Geldanamycin and 10 mM L-NAME. Participants completed both protocols during the early follicular (low hormone) phase of the menstrual cycle (0-7 days). Protocol 1: participants rested in the heat (35°C) for 70 min and then performed 50 min of moderate-intensity cycling (~55% VO2peak ) followed by 30 min of recovery. Protocol 2: participants were passively heated to increase rectal temperature by 1.0°C, comparable to end-exercise. HSP90 inhibition attenuated CVC%max relative to control at end-exercise (p < .05), but not during passive heating. While NOS inhibition and combined HSP90 + NOS inhibition attenuated CVC%max relative to control for both protocols (all p < .05), they did not differ from each other. We show that HSP90 modulates cutaneous vasodilation NOS-dependently during exercise in young women, with no effect during passive heating, despite a similar NOS contribution.

Keywords: heat loss; microcirculation; oestrogen; sex; skin blood flow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Benzoquinones / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Exercise*
  • Female
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism*
  • Hot Temperature*
  • Humans
  • Lactams, Macrocyclic / pharmacology
  • Microcirculation / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Skin / blood supply
  • Vasodilation*


  • Benzoquinones
  • Enzyme Inhibitors
  • HSP90 Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester
  • geldanamycin