Endothelins and the cerebral circulation.

Information about the presence of the endothelin system in the cerebrovascular bed and its physiological or pathophysiological role(s) in the control of the cerebral circulation has dramatically increased in recent years. Endothelin-1 can be produced in the cerebrovascular bed from circulating big endothelin or by endogenous endothelin mRNA expression. Endothelins bind to specific ETA and ETB receptors in cerebral vessels. Activation of these receptors triggers intracellular signal transduction mechanisms mediating tone maintenance as well as long-term vascular changes. Endothelins are potent constrictors of cerebral arteries isolated from different species, including humans. In vivo the reductions in vessel diameter or blood flow due to the direct vasoconstrictive effects of endothelin-1 are modulated or even changed in some cases to opposite vasodilatative effects because of the release of dilatative substances. The ability of locally applied endothelin-1 to reduce blood flow to pathologically low levels has been used to develop animal models of focal cerebral ischemia. Endothelin-1 is thought to play a role in the pathophysiology of nonhemorrhagic cerebral infarct and in cerebral vasospasm after subarachnoid hemorrhage.