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

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.