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Deficiency of TRPV4 abolishes shear stress‐induced vasodilation in mice.
Author(s) -
Köhler Ralf,
Hartmannsgruber Veronika,
Heyken WillmThomas,
Kacik Michael,
Grgic Ivica,
Harteneck Christian,
Liedtke Wolfgang,
Hoyer Joachim
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.937.3
Subject(s) - trpv4 , vasodilation , chemistry , endothelium , medicine , endocrinology , transient receptor potential channel , pharmacology , biochemistry , receptor
In endothelial sensing of shear stress, the Ca2+‐permeable TRPV4 channel was proposed a candidate mechanosensor. Using TRPV4−/− mice, we investigated whether the absence of endothelial TRPV4 alters shear‐stress‐induced vasodilation. Loss of the TRPV4 protein and function was confirmed by IHC and electrophysiology in endothelium of TRPV4−/− mice. Agonist‐ and shear stress‐induced vasodilation was determined by pressure myography in carotid artery (CA) of TRPV4−/− and TRPV4+/+ mice (WT). In WT CAEC, TRPV4 was activated by the pharmacological TRPV4‐opener 4alphaPDD, arachidonic acid (AA), and by hypotonic cell swelling (HTS). In CAEC of TRPV4−/−, 4alphaPDD did not produce currents and currents in response to AA and HTS were greatly reduced. 4alphaPDD elicited a robust and strictly endothelium‐dependent vasodilation in WT mice, again strikingly absent in TRPV4−/− mice. Shear stress‐induced vasodilation was present in WT, but was eliminated in TRPV4−/− mice. Flow‐induced vasodilation was significantly reduced in TRPV4−/− vs. WT mice. In conclusion, loss of TRPV4 abolishes shear stress‐induced vasodilation. Thus, Ca2+‐influx through endothelial TRPV4 channels is a critical mechanism contributing to endothelial mechanotransduction.