Role of Transient Receptor Potential Vanilloid 4 in Vascular Function

FIGURE 1. The effect of transient receptor potential vanilloid 4 (TRPV4) on vasculature. TRPV4 channels can be activated by stimuli-sensing, endogenous agonists, and exogenous agonists. The activation of TRPV4 participates in the regulation of vascular dilation and constriction, vascular permeability, vascular remolding, and vascular damage, playing important roles in vascular related diseases.

FIGURE 2. The underlying mechanisms of the regulation of TRPV4 in vasodilation. In the vascular endothelial cells, TRPV4 can be activated by stimuli-sensing, G protein-coupled receptors (GPCR) activation, epoxyeicosatrienoic acid (EETs), GSK1016790A (GSK), and 4α-PDD. Its activation leads to Ca2+ influx and the subsequent activation of nitric oxide synthase (NOS), cyclooxygenase (COX), and intermediate-conductance Ca2+-sensitive K+ channels/small conductance Ca2+-sensitive K+ channels (IKCa/SKCa) channels to induce nitric oxide (NO), prostacyclin (PGI2), and endothelial-derived hyperpolarizing factor (EDHF) production, respectively, and causes vasodilation. In smooth muscles, TRPV4 can be activated by endothelial-derived EETs or chemical agonists, leading to Ca2+ entry-induced Ca2+ release from ryanodine receptor (RyR) in the sarcoplasmic reticulum (SR), the stimulation of Ca2+ sparks, and the subsequent activation of KCa1.1 to stimulate smooth muscle hyperpolarization and vasodilation.