Effect of endothelin receptor antagonists on non-muscle matrix compaction in a cell culture vasospasm model

• Published in: Neurological research (New York) 2000-03, Vol.22 (2), p.209-214
• Main Authors: Ogihara, K., Barnanke, D.H., Zubkov, A.Y., Parent, A.D., Zhang, J.H.
• Format: Article
• Language: English
• Subjects: Azepines - pharmacology; Cells, Cultured; Cerebral vasospasm; Cerebrospinal Fluid - physiology; Collagen - drug effects; Collagen lattice; Endothelin receptor; Endothelin Receptor Antagonists; Endothelin-1 - pharmacology; Erythrocytes - physiology; Extracellular Matrix - drug effects; Extracellular Matrix - physiology; Fibroblasts - drug effects; Humans; Oligopeptides - pharmacology; Piperidines - pharmacology; Receptor, Endothelin A; Receptor, Endothelin B; Subarachnoid hemorrhage; Vasospasm, Intracranial - blood; Vasospasm, Intracranial - cerebrospinal fluid; Vasospasm, Intracranial - physiopathology
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2000.11741063

Endothelin-1 (ET-1), a potent vascular smooth muscle constrictor, is one of the possible spasmogens in cerebral vasospasm. However, the role of ET-I in non-muscle compaction (another aspect of the pathogenesis of cerebral vasospasm) has not been reported. This study was undertaken to demonstrate the effect of ET-I, as well as erythrocyte lysate and bloody cerebrospinal fluid (CSF), on fibroblast populated collagen lattice (FPCL) compaction. Human dermal fibroblasts were used to form FPCL. The concentration- dependent effect of ET-I was examined in the absence and presence of an ETA receptor antagonist (BQ- 485), or an ETB receptor antagonist (BQ-788), or both. FPCL compaction was determined by measuring reduction of areas over five days following treatment. To compare the effect of ET-1 on lattice compaction, erythrocyte lysate and bloody CSF obtained from a cerebral vasospasm patient were also tested. We found that ET-1 increased FPCL compaction in a concentration-dependent (but not time-dependent) manner. Erythrocyte lysate produced the strongest compaction, however, without time-dependence. Bloody CSF promoted FPCL compaction in a time-dependent fashion. Compaction induced by ET-1 was inhibited by BQ-485 but not by BQ-788. We concluded that ET-1 promotes FPCL compaction by activation of ETA receptors. Other components in bloody CSF or erythrocytes may also contribute to FPCL compaction. [Neurol Res 2000; 22: 209-214]