Role of bradykinin type 2 receptors in human sweat secretion: Translational evidence does not support a functional relationship

Thad E. Wilson, Seetharam Narra, Kristen Metzler-Wilson, Artur Schneider, Kelsey A. Bullens, Ian S. Holt

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46-48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer's) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.

Original languageEnglish
Pages (from-to)162-166
Number of pages5
JournalSkin Pharmacology and Physiology
Volume34
Issue number3
DOIs
StatePublished - Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 S. Karger AG. All rights reserved.

Keywords

  • Bradykinin type 2 receptors
  • HOE-140
  • Intradermal microdialysis
  • Kallikrein-kinin system

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Dermatology

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