Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers

J Anesth. 2009;23(4):620-3. doi: 10.1007/s00540-009-0786-8. Epub 2009 Nov 18.

Abstract

We previously reported that desflurane induced airway contraction via antidromic tachykinin release from sensory C-fibers. Here, we investigated the effect of desflurane on airway lung resistance (R(L)) using specific receptor antagonists in C-fibers. Young guinea pigs were anesthetized and their tracheas were cannulated with an endotracheal tube via a tracheotomy. A Fleisch pneumotachograph and a differential transducer were used to monitor respiratory flow rate, intrapleural pressure, and airway pressure, and R(L) was calculated and recorded. A transient receptor potential A1 (TRPA1) or a transient receptor potential V1 (TRPV1) selective antagonist of sensory C-fibers, i.e., HC030031 or BCTC, was administered before the exposure to desflurane. In an additional experiment, tachykinin receptor of airway smooth muscles was antagonized only by the neurokinin-2 receptor antagonist MEN-10376 before the exposure to desflurane. HC030031 completely inhibited both the first and the second contractile responses induced by desflurane, whereas BCTC had little effect. MEN-10376 also significantly and substantially diminished the contractile response. Desflurane contracts the airway in untreated guinea pigs mainly by activating irritant gas receptor TRPA1 of afferent C-fibers, resulting in the release of contractile tachykinins such as neurokinin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Resistance / drug effects*
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Desflurane
  • Guinea Pigs
  • Isoflurane / analogs & derivatives*
  • Isoflurane / pharmacology
  • Male
  • Nerve Fibers, Unmyelinated / drug effects*
  • Receptors, Neurokinin-2 / drug effects
  • Sensory Receptor Cells / drug effects*
  • TRPC Cation Channels / drug effects*
  • Tachykinins / metabolism

Substances

  • Anesthetics, Inhalation
  • Receptors, Neurokinin-2
  • TRPC Cation Channels
  • Tachykinins
  • transient receptor potential cation channel, subfamily C, member 1
  • Desflurane
  • Isoflurane