Vascular physiology of a Ca2+ mobilizing second messenger - cyclic ADP-ribose.

Cyclic ADP-ribose (cADPR) is a novel Ca(2+) mobilizing second messenger, which is capable of inducing Ca(2+) release from the sarcoplasmic reticulum (SR) via activation of ryanodine receptors (RyR) in vascular cells. This signaling nucleotide has also been reported to participate in generation or modulation of intracellular Ca(2+) sparks, Ca(2+) waves or oscillations, Ca(2+)- induced Ca(2+) release (CICR) and spontaneous transient outward currents (STOCs) in vascular smooth muscle cells (VSMCs). With respect to the role of cADPR-mediated signaling in mediation of vascular responses to different stimuli, there is accumulating evidence showing that cADPR is importantly involved in the Ca(2+) response of vascular endothelial cells (ECs) and VSMCs to various chemical factors such as vasoactive agonists acetylcholine, oxotremorine, endothelin, and physical stimuli such as stretch, electrical depolarization and sheer stress. This cADPR-RyR-mediated Ca(2+) signaling is now recognized as a fundamental mechanism regulating vascular function. Here we reviewed the literature regarding this cADPR signaling pathway in vascular cells with a major focus on the production of cADPR and its physiological roles in the control of vascular tone and vasomotor response. We also summarized some publish results that unveil the underlying mechanisms mediating the actions of cADPR in vascular cells. Given the importance of Ca(2+) in the regulation of vascular function, the results summarized in this brief review will provide new insights into vascular physiology and circulatory regulation.