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.
Ogihara
K
K
Department of Neurosurgery, University of Mississippi Medical Center, Jackson 39216, USA.
Barnanke
D H
DH
Zubkov
A Y
AY
Parent
A D
AD
Zhang
J H
JH
D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000502:physiology; D003094:Collagen / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D004912:Erythrocytes / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D020301:Vasospasm, Intracranial / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*
D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C083116:BQ 485; C086539:BQ 788; D003094:Collagen