| Research Abstract |
Endothelin, a recently discovered peptide produced by endothelin cells, has been shown to have potent constrictor effects on major arteries in vitro. This experiment was performed to determine whether endothelin plays a physiological role in cerebral vasospasm after subarachnoid hemorrhage. A cisternal injection of endothelin 1 caused severe vasoconstriction of the canine basilar artery. The degree of vasoconstriction was dose related and long lasting, persisting for more than 24 hours. This constriction was prevented completely pretreatment with nicardipine. Endothelin 1 produced a marked and transient elevation on blood pressure.
We also investigated the histological changes between arteries constricted by endothelin 1 for 7 days and vasospastic arteries induced by the double injection of autologous blood. Group 1 was a shamーoperated group. Group 2 animals received a continuous cisternal injection of endothelin 1 (1.7 X 10-9mo1/7days) by a miniosmotic pump implanted in the neck musculature for 7 days. Group 3 received double injections of cisternal blood administered 48 hours apart. Angiography showed severe constriction of the basilar artery, 34.6% and 43% on Groups 2 and 3, respectively, on Day 7. Histological study showed marked constriction of the basilar artery in both Group 2 and Group 3. Degenerative changes in endothelial cells and smooth muscle cells were observed in both Group 2 and Group 3. Immunohistochemical study demonstrated endothelin 1 in the endothelial cells in Group 2, but not on Group 1 or in Group 3. It is suggested that endothelin 1 may play an important role in the pathogenesis of cerebral vasospasm.
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