Localization and Alteration of Immunoreactive Endothelin-1 in Canine Basilar Arteries Following Subarachnoid Hemorrhage

Localization and alteration of the levels of immunoreactive endotheoin-1 (ir-ET-1) products of canine basilar artery were examined in a one-hemorrhage model. Subarachnoid hemorrhage (SAH) was induced by a single injection of autologous arterial blood into the cisterna magna. In SAH dogs, the endothelial cells on day 2 showed minimal changes such as rounding nuclei or edema, and these injuries progressed on days 4 to 6 from moderate changes with subendothelial edema to severe damage characterized by denudation. In these dogs, ir-ET-1 products on endothelial cells were significantly enhanced and reached maximum levels on day 2 followed by gradual reduction on day 4 to 6. Although no significant changes appeared on endothlial cells in untreated dogs and control dogs on day 2 after the injection of saline, weak ir-ET-1 products were localized irregularly on those cells. However, ir-ET-1 levels on day 4 and 6 were significantly higher in SAH dogs than in untreated dogs. Cerebral arteries were covered with blood clots and a number of inflammatory cells had invaded the adventitia of basilar arteries, in addition to sorrounding the clots. The number of inflammatory cells and the quantity of ir-ET-1 products in the adventitia achieved maximum levels on day 2, and decreased on day 4 to 6. Almost all the inflammatory cells were positive for anti-macrophage antibody. Thus, the levels of ir-ET-1 products on endothelial cells were enhanced with minimal injury on day 2 and gradually decreased with the progression of the injury, while those in the adventitia correlated well with the number of macrophages migrating into the adventitia. These results suggest that ET-1 is derived mainly from macrophages migrating into adventitia as well as endothelial cells, and is an important factor for vasospasm after SAH, not only in the early phase but also in the late stages.