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

Endothelin-1 (ET-1), a potent vascular smooth muscle constrictor, is one of the possible spasmogens in cerebral vasospasm. However, the role of ET-1 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-1, 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-1 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.