Calcium and endothelium-mediated vasodilator signaling

Vascular tone refers to the balance between arterial constrictor and dilator activity. The mechanisms that underlie tone are critical for the control of haemodynamics and matching circulatory needs with metabolism, and thus alterations in tone are a primary factor for vascular disease etiology. The dynamic spatiotemporal control of intracellular Ca(2+) levels in arterial endothelial and smooth muscle cells facilitates the modulation of multiple vascular signaling pathways. Thus, control of Ca(2+) levels in these cells is integral for the maintenance of tone and blood flow, and intimately associated with both physiological and pathophysiological states. Hence, understanding the mechanisms that underlie the modulation of vascular Ca(2+) activity is critical for both fundamental knowledge of artery function, and for the development of targeted therapies. This brief review highlights the role of Ca(2+) signaling in vascular endothelial function, with a focus on contact-mediated vasodilator mechanisms associated with endothelium-derived hyperpolarization and the longitudinal conduction of responses over distance.