Transient receptor potential channel activation and endothelium-dependent dilation in the systemic circulation.
The endothelium plays a crucial role in the regulation of vascular tone by releasing a number of vasodilator mediators, including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor(s). The production of these mediators is typically initiated by an increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in endothelial cells. An essential component of this Ca(2+) signal is the entry of Ca(2+) from the extracellular space through plasma membrane Ca(2+)-permeable channels. Although the molecular identification of the potential Ca(2+) entry channel(s) responsible for the release of endothelial relaxing factors is still evolving, accumulating evidence indicates that the transient receptor potential (TRP) channels, a superfamily of Ca(2+)-permeable cation channels, serve as an important mechanism of Ca(2+) entry in endothelial cells and other nonexcitable cells. The activation of these channels has been implicated in diverse endothelial functions ranging from control of vascular tone and regulation of vascular permeability to angiogenesis and vascular remodeling. This review summarizes recent evidence concerning TRP channels and endothelium-dependent dilation in several systemic vascular beds. In particular, we highlight the emerging roles of several TRP channels from the canonical and vanilloid subfamilies, including TRPV4, TRPC4, and TRPC6, in vasodilatory responses to shear stress and receptor agonists and discuss potential signaling mechanisms linking the TRP channel activation and the initiation of endothelium-derived hyperpolarizing factor-mediated responses in endothelial cells.
Zhang
David X
DX
Department of Medicine, Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Rd Milwaukee, WI 53226, USA. xfzhang@mcw.edu
Gutterman
David D
DD
D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D001783:Blood Flow Velocity / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
D050051:Transient Receptor Potential Channels