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Evidence for a functional role of endothelial TRPV4 in shear stress‐induced vasodilatation
Author(s) -
Koehler Ralf,
Grgic Ivica,
Heyken Willm,
Heinau Philipp,
Busch Christoph,
Schubert Rudolf,
Maier Tanja,
Hoyer Joachim
Publication year - 2006
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.20.5.a1116
Subject(s) - myograph , trpv4 , vasodilation , chemistry , endothelium , medicine , biophysics , endocrinology , microbiology and biotechnology , biochemistry , biology , transient receptor potential channel , receptor
Ca2+‐influx through TRP channels is believed to play a role in the synthesis of endothelial vasodilators. Here, we investigated function and expression of the TRPV4 channel in endothelial cells (EC) by using the in situ patch‐clamp technique, single‐cell‐RT‐PCR, Ca2+‐imaging, and pressure‐myograph experiments. In EC in situ, TRPV4‐like currents were activated by the selective TRPV4‐opener 4α‐phorbol‐12,13‐didecanoate (4αPDD), arachidonic acid (AA), moderate warmth, and hypotonic stress. Single‐cell‐RT‐PCR revealed expression of TRPV4, but none of the other closely related TRPV1‐3. Activation of this endothelial TRPV4 by 4αPDD increased intracellular [Ca2+]i to 250 nM. In pressure‐myograph experiments in carotid artery (CA) and small A. gracilis, intraluminal application of 4αPDD caused a robust vasodilatation by ≈80% (at 1 uM; KD 0.3 uM) which was strictly endothelium‐dependent and was suppressed by the TRPV4‐inhibitor ruthenium red (RuR). Wall shear stress (WSS)‐induced vasodilatation was similarly blocked by RuR and was also prevented by inhibition of phospholipase A2 by AACOCF3. In the presence of inhibitors of NO‐ and prostacyclin‐synthesis, 4αPDD and WSS did not produce considerable vasodilatation of CA whereas 4αPDD but not WSS caused vasodilatation of small A. gracilis. In conclusion, Ca2+‐entry through endothelial TRPV4 channels triggers NO‐ and EDHF‐dependent vasodilatation in rat endothelium. Since blockage of TRPV4 suppressed WSS‐induced vasodilatation, TRPV4 seems to play a role in endothelial mechanosensing of WSS.