title: Evidence for a functional role of endothelial transient receptor potential V4 in shear stress-induced vasodilatation.
abstract: OBJECTIVE
  Ca2+-influx through transient receptor potential (TRP) channels was proposed to be important in endothelial function, although the precise role of specific TRP channels is unknown. Here, we investigated the role of the putatively mechanosensitive TRPV4 channel in the mechanisms of endothelium-dependent vasodilatation.
  
  
  RESULTS
  Expression and function of TRPV4 was investigated in rat carotid artery endothelial cells (RCAECs) by using in situ patch-clamp techniques, single-cell RT-PCR, Ca2+ measurements, and pressure myography in carotid artery (CA) and Arteria gracilis. In RCAECs in situ, TRPV4 currents were activated by the selective TRPV4 opener 4alpha-phorbol-12,13-didecanoate (4alphaPDD), arachidonic acid, moderate warmth, and mechanically by hypotonic cell swelling. Single-cell RT-PCR in endothelial cells demonstrated mRNA expression of TRPV4. In FURA-2 Ca2+ measurements, 4alphaPDD increased [Ca2+]i by &140 nmol/L above basal levels. In pressure myograph experiments in CAs and A gracilis, 4alphaPDD caused robust endothelium-dependent and strictly endothelium-dependent vasodilatations by &80% (K(D) 0.3 microL), which were suppressed by the TRPV4 blocker ruthenium red (RuR). Shear stress-induced vasodilatation was similarly blocked by RuR and also by the phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone (AACOCF3). 4alphaPDD produced endothelium-derived hyperpolarizing factor (EDHF)-type responses in A gracilis but not in rat carotid artery. Shear stress did not produce EDHF-type vasodilatation in either vessel type.
  
  
  CONCLUSIONS
  Ca2+ entry through endothelial TRPV4 channels triggers NO- and EDHF-dependent vasodilatation. Moreover, TRPV4 appears to be mechanistically important in endothelial mechanosensing of shear stress.
authors: Department of Internal Medicine-Nephrology, Philipps-University, Baldingerstrasse, 35033 Marburg, Germany. rkoehler@med.uni-marburg.de
authors: Ralf
authors: R
authors: Köhler
authors: Willm-Thomas
authors: WT
authors: Heyken
authors: Philipp
authors: P
authors: Heinau
authors: Rudolf
authors: R
authors: Schubert
authors: Han
authors: H
authors: Si
authors: Michael
authors: M
authors: Kacik
authors: Christoph
authors: C
authors: Busch
authors: Ivica
authors: I
authors: Grgic
authors: Tanja
authors: T
authors: Maier
authors: Joachim
authors: J
authors: Hoyer