Mechanisms of disease: roles of nitric oxide and endothelin-1 in delayed cerebral vasospasm produced by aneurysmal subarachnoid hemorrhage.

Molecular biologic investigations in the past decades have begun to unravel the intracellular mechanisms involved in vasomotor regulation of cerebral blood vessels and their failure in delayed cerebral vasospasm produced by aneurysmal subarachnoid hemorrhage. Progress in deciphering macrovascular regulatory mechanisms and their failure in delayed cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage have revealed that there are at least two important vasoactive substances-nitric oxide and endothelin-1-that play important roles in the clinical manifestations of subarachnoid-hemorrhage-induced cerebral vasospasm. Nitric oxide is a cell-membrane-permeable free radical gas that accounts for the phenomenon of vasodilatation by a variety of vasodilator agents. Endothelin-1, a 21 amino acid peptide, is one of the most potent constricting factors. Cerebral vasospasm is thought to represent a disturbance in the cerebral vasomotor equilibrium for which these two physiologically antagonistic compounds are at least partly responsible. Advances in our understanding of the molecular responses of the cerebral vasculature to subarachnoid hemorrhage should lead to more comprehensive management as knowledge becomes translated into development of effective pharmacologic agents to reverse or prevent cerebral vasospasm following aneurysmal subarachnoid hemorrhage.