A variety of factors interact to regulate vascular tone and thereby control blood flow to the regional circulations. The influx of calcium into vascular smooth muscle initiates contraction by binding to calmodulin and stimulating myosin light chain kinase. With the phosphorylation of the myosin light chain, myosin can interact with actin, hydrolyze ATP and produce contraction. Vascular relaxation can occur by reducing intracellular calcium or by dephosphorylating the myosin light chain. Endogenous vasodilators can promote vascular smooth muscle relaxation at three major sites, the noradrenergic nerve terminal, the smooth muscle cell, and the vascular endothelium. The release of norepinephrine from sympathetic nerves can be inhibited directly by the products of local metabolic activity and through the stimulation of a number of presynaptic receptors (for example, purinergic1, alpha2, cholinergic muscarinic). Many vasodilator agonists may use the endothelium to produce their effect (for example, acetylcholine, serotonin, thrombin, and the like). It is postulated that these agents cause endothelial calcium influx, thereby activating phospholipase to produce arachidonic acid, the majority of which is processed through the lipoxygenase pathway. It has been suggested that a lipoxygenase product stimulates the production of cyclic GMP, one controller of vascular smooth muscle calcium concentration. Each vascular bed has its own unique composition of local, neurogenic, and humoral blood flow regulatory mechanisms. Each vascular bed is also controlled by a broader integrated circulatory control scheme involving the central nervous system through reflex arcs and hormonal production. An understanding of the local factors regulating vascular tone, and how they are integrated within a global cardiocirculatory control system