Endothelial Ca(2+) signaling-dependent vasodilation through transient receptor potential channels

Ca(2+) signaling of endothelial cells plays a critical role in controlling blood flow and pressure in small arteries and arterioles. As the impairment of endothelial function is closely associated with cardiovascular diseases (e.g., atherosclerosis, stroke, and hypertension), endothelial Ca(2+) signaling mechanisms have received substantial attention. Increases in endothelial intracellular Ca(2+) concentrations promote the synthesis and release of endothelial-derived hyperpolarizing factors (EDHFs, e.g., nitric oxide, prostacyclin, or K(+) efflux) or directly result in endothelial-dependent hyperpolarization (EDH). These physiological alterations modulate vascular contractility and cause marked vasodilation in resistance arteries. Transient receptor potential (TRP) channels are nonselective cation channels that are present in the endothelium, vascular smooth muscle cells, or perivascular/sensory nerves. TRP channels are activated by diverse stimuli and are considered key biological apparatuses for the Ca(2+) influx-dependent regulation of vasomotor reactivity in resistance arteries. Ca(2+)-permeable TRP channels, which are primarily found at spatially restricted microdomains in endothelial cells (e.g., myoendothelial projections), have a large unitary or binary conductance and contribute to EDHFs or EDH-induced vasodilation in concert with the activation of intermediate/small conductance Ca(2+)-sensitive K(+) channels. It is likely that endothelial TRP channel dysfunction is related to the dysregulation of endothelial Ca(2+) signaling and in turn gives rise to vascular-related diseases such as hypertension. Thus, investigations on the role of Ca(2+) dynamics via TRP channels in endothelial cells are required to further comprehend how vascular tone or perfusion pressure are regulated in normal and pathophysiological conditions.