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

Skin Pharmacol Physiol. 2019;32(5):235-243. doi: 10.1159/000500643. Epub 2019 Jun 20.


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.

Keywords: Elderly; Inflammation; Microcirculation; Thermoregulation; Trypsin.

MeSH terms

  • Aged
  • Exercise / physiology*
  • Hot Temperature
  • Humans
  • Male
  • Middle Aged
  • Oligopeptides / pharmacology
  • Receptor, PAR-2 / agonists
  • Receptor, PAR-2 / physiology*
  • Skin Physiological Phenomena
  • Sweating / drug effects
  • Sweating / physiology*
  • Vasodilation / drug effects
  • Vasodilation / physiology*


  • F2RL1 protein, human
  • Oligopeptides
  • Receptor, PAR-2
  • seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide