Effect of endothelin receptor antagonists on non-muscle matrix compaction in a cell culture vasospasm model
Effect of endothelin receptor antagonists on non-muscle matrix compaction in a cell culture vasospasm model
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DOI：
10.1080/01616412.2000.11741063
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发表时间：
2000-03
影响因子：
1.9
通讯作者：
K. Ogihara;D.H. Barnanke;A. Zubkov;A. Parent;J.H. Zhang
中科院分区：
文献类型：
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作者：
K. Ogihara;D.H. Barnanke;A. Zubkov;A. Parent;J.H. Zhang
摘要内皮素-1(ET-1)是一种强有力的血管平滑肌收缩因子，可能是脑血管痉挛的促痉剂之一。然而，ET-I在非肌肉紧实(脑血管痉挛发病机制的另一个方面)中的作用尚未见报道。本研究旨在探讨ET-I以及红细胞裂解液和血性脑脊液对成纤维细胞填充的胶原网(FPCL)致密化的影响。用人真皮成纤维细胞形成FPCL。在ETA受体拮抗剂(BQ-485)和/或ETB受体拮抗剂(BQ-788)存在和不存在的情况下，检测ET-I的浓度依赖效应。通过测量治疗后5天以上面积的缩小来确定FPCL的紧实度。为了比较ET-1对晶格紧凑的影响，还检测了一例脑血管痉挛患者的红细胞裂解液和血脑脊液。我们发现ET-1以浓度依赖(但不是时间依赖)的方式增加FPCL的紧实度。然而，红细胞裂解物产生了最强的紧实度，没有时间依赖性。血脑脊液以时间依赖的方式促进FPCL的致密化。BQ-485能抑制ET-1的致密化，但BQ-788不能抑制ET-1的致密化。我们的结论是，ET-1通过激活ETA受体促进FPCL紧致。血脑脊液或红细胞中的其他成分也可能是FPCL致密的原因。Neurol Res 2000；22：209-214
Abstract 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]