Endothelium-derived Vasoactive Factors and Regulation of the Cerebral Circulation

Vasoactive factors produced and released by endothelium exert a powerful influence on vascular tone in the cerebral circulation. Endothelium-derived relaxing factor (EDRF), which has been identified as nitric oxide (NO) or an NO-containing compound, is produced under basal conditions in cerebral blood vessels. EDRF mediates endothelium-dependent relaxation in response to a number of stimuli in the cerebral circulation. The influence of NO on the cerebral circulation appears to be particularly important and complex because both neurons and glia, in addition to endothelium, produce NO in response to some stimuli. Neuronally derived NO may mediate local vasodilation in response to increased neuronal activity. In addition to EDRF, cerebral endothelium may produce other relaxing factors, including prostacyclin, endothelium-derived hyperpolarizing factor, and oxygen-derived free radicals. Several pathophysiological conditions are associated with impaired endothelium-dependent responses that may involve the decreased production of EDRF and release of endothelium-derived contracting factors, such as the cyclooxygenase products of arachidonic acid and endothelin. The release of endothelin, an extremely potent and long-lasting vasoconstrictor peptide, may contribute to vasospasm after subarachnoid hemorrhage.