Enhanced Secretion of Endothelin by Endothelial Cells in Response to Hemoglobin

Confluent cultures of bovine aortic endothelium in serum-free medium were exposed to increasing concentrations (10-6-10-4 M) of freshly prepared erythrocyte lysates (primarily hemoglobin). Hemoglobin increased endothelin-1 secretion into the medium in a dose-dependent manner after 24 hours. The enhanced secretion of endothelin-1 in response to hemoglobin was sustained for 72 hours, suggesting active production and secretion of endothelin-1 rather than release from intracellular pools. Secreted endothelin-1 in the medium was characterized by high-performance liquid chromatography coupled with radioimmunoassay. Endothelin-1, a potent and long-lasting vasoconstrictor, may be one of the causative factors of cerebral vasospasm after subarachnoid hemorrhage. Oxyhemoglobin, derived from periarterial clot, may play an important role in the secretion of endothelin-1 in cerebral vasospasm.