TRPV4 channel‐mediated Ca2+ entry and vasodilation in small bovine coronary arteries

Emerging evidence indicates that the vanilloid subfamily of transient receptor potential channels, member 4 (TRPV4) is activated by shear stress leading to Ca2+‐influx in vascular endothelial cells. Activation of TRPV4 may represent a novel mechanism by which shear stress activates endothelial cells to induce arterial dilation. We investigated the role of TRPV4 channel in vasomotor responses of small bovine coronary arteries (BCA). Using immunoblots, TRPV4 protein was detected in coronary endothelial cells. Using a Ca2+ assay with fura‐2, 4a‐phorbol‐12,13‐didecanoate (4αPDD, 5 mM), a selective TRPV4 opener, increased intracellular Ca2+ ([Ca2+]i) in endothelial cells (mean increase above basal or Δ[Ca2+]i of 153±6.0 nM; n=3), a response that was inhibited by removing extracellular Ca2+ (Δ[Ca2+]i of 20±2.4 nM) or by the TRPV4 blocker ruthenium red (RuR) (Δ[Ca2+]i of 55±5.4 nM). In isolated and cannulated BCA, 4aPDD (50 nM‐5 mM) elicited concentration‐dependent relaxations (maximal relaxation of 55±8%; n=4). Shear stress (10–150 ml/min) dilated BCA (maximal relaxation of 59±11%; n=4), which were inhibited by RuR (6±10%). It is concluded that TRPV4 channels are expressed in BCA and activation of these channels induces endothelial Ca2+ influx and arterial relaxation. TRPV4 channels may play a role in endothelial shear sensing and flow‐induced dilation in these arteries.