Figure 6From: Targeted over-expression of endothelin-1 in astrocytes leads to more severe brain damage and vasospasm after subarachnoid hemorrhageProposed mechanism of astrocytic ET-1 mediated cerebral vasospasm after SAH. GET-1 mice with over-expressed in ET-1 showed more severe neurological deficits and vasospasm after SAH. Increased astrocytic ET-1 during SAH induces cerebral vasospasm through the ETA receptor and mediated by PKC-α, which leads to dynfunction in the K+ channels. Administration of ETA receptor antagonist ABT-627 ameliorates the SAH-induced vasospasm. The impairment of NO system also exaggerates the vasospasm effect. Astrocytic ET-1 leads to more severe cerebral edema and BBB breakdown that further contributes to cerebral vasoconstriction. Vasopressin V1a receptor antagonist, SR 49059, significantly reduced the SAH-induced edema, suggesting that astrocytic ET-1 induces edema in SAH through vasopressin V1a receptor.Back to article page