Transient receptor potential vanilloid 4 gene-deficiency attenuates the inhibitory effect of 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid on vascular permeability in mice

J Pharmacol Sci. 2025 Jan;157(1):35-38. doi: 10.1016/j.jphs.2024.11.005. Epub 2024 Nov 28.

Abstract

We investigated whether an anti-inflammatory lipid metabolite named 5,6-DiHETE reduces vascular permeability by inhibiting TRPV4 channels in vivo. In wild-type (WT) mice, histamine-induced dye extravasation was reduced by pre-administration of 5,6-DiHETE. In TRPV4-deficient mice, extravasation and histamine-induced edema were already reduced, and 5,6-DiHETE had no additional effect. In isolated WT aortas, 5,6-DiHETE attenuated acetylcholine-induced relaxation, but this effect was absent in TRPV4-deficient aortas. These findings suggest that 5,6-DiHETE reduces vascular permeability by inhibiting TRPV4 activity.

Keywords: 5,6-DiHETE; TRPV4; Vascular permeability.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Aorta / drug effects
  • Aorta / metabolism
  • Arachidonic Acids / pharmacology
  • Capillary Permeability* / drug effects
  • Edema / drug therapy
  • Edema / genetics
  • Histamine / metabolism
  • Histamine / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • TRPV Cation Channels* / deficiency
  • TRPV Cation Channels* / genetics
  • TRPV Cation Channels* / metabolism

Substances

  • TRPV Cation Channels
  • Trpv4 protein, mouse
  • Histamine
  • Arachidonic Acids
  • Anti-Inflammatory Agents