EDN1 and hemorrhagic stroke: Although many studies have reported that ET-1 levels are increased in plasma and CSF during ischemic and hemorrhagic stroke [56,57], it is still unclear whether the production and release of ET-1 is the primary response of the brain cells (astrocytes, endothelial cells, neurons) to the stroke, or the secondary response in which activation of the sympathoadrenal system increases the plasma catecholamine and vasopressin levels [58], which stimulates the release of ET-1 from the peripheral organs.