Endothelin Receptor Subtypes in the Pathogenesis of Angioplasty‐Induced Neointima Formation in the Rat: A Comparison of Selective ETA Receptor Antagonism and Dual ETA/ETB Receptor Antagonism Using BQ‐123 and SB 209670
Endothelin Receptor Subtypes in the Pathogenesis of Angioplasty‐Induced Neointima Formation in the Rat: A Comparison of Selective ETA Receptor Antagonism and Dual ETA/ETB Receptor Antagonism Using BQ‐123 and SB 209670
复制标题
血管成形术诱导的大鼠新内膜形成发病机制中的内皮素受体亚型：使用 BQ-123 和 SB 209670 比较选择性 ETA 受体拮抗作用和双重 ETA/ETB 受体拮抗作用
DOI：
10.1097/00005344-199506263-00056
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发表时间：
1995
影响因子：
3
通讯作者：
E. Ohlstein
中科院分区：
文献类型：
--
作者：
S. Douglas;L. Vickery;C. Louden;J. D. Elliott;E. Ohlstein
总结：本研究比较了急性和慢性内皮素（ET）ETA或双重ETA/B受体拮抗剂在大鼠颈总动脉（RCCA）模型中使用BQ-123和SB 209670的血管保护作用。在血管成形术时，急性动脉内输注（0.1 mg/kg/min）BQ-123或SB 209670 2 h未减弱血管成形术后2周观察到的新生内膜病变形成（新生内膜：中膜比率分别为对照的137%和116%）。相比之下，SB 209670的长期给药（推注i. p.注射，2.5 mg/kg b.i.d.）减少损伤形成（相对于载体对照，新生内膜：中膜比率被抑制52%; p < 0.05）。BQ-123的相同剂量方案未表现出显著的血管保护作用（新生内膜：中膜比率为128%媒介物对照）。然而，BQ-123的该剂量方案与显著的和选择性的ETA受体拮抗作用相关。对外源性ET-1给药的全身性升压反应被抑制91%（p < 0.05），而相关的降压反应与在溶剂处理的大鼠中观察到的没有差异。因此，由于长期给予药理学剂量的ETA选择性拮抗剂BQ-123不能防止RCCA模型中的损伤形成，而ETA/B受体拮抗剂SB 209670具有血管保护作用，因此数据暗示了ET B受体亚型在大鼠新生内膜形成的发病机制中的重要作用，无论是单独的还是与ETA受体活化一致的。
Summary: The present study compared the vasculo-protective efficacy of acute and chronic endothelin (ET) ETA or dual ETA/B receptor antagonism in the rat common carotid artery (RCCA) model using BQ-123 and SB 209670. Acute intra-arterial infusion (0.1 mg/kg/min) for 2 h at the time of angioplasty of either BQ-123 or SB 209670 did not attenuate the neointima lesion formation observed 2 weeks after angioplasty (neointima: media ratios of 137% and 116% of control, respectively). In contrast, chronic administration of SB 209670 (bolus i.p. injection, 2.5 mg/kg b.i.d.) attenuated lesion formation (neointima: media ratio inhibited by 52% relative to vehicle control; p < 0.05). An identical dosage regimen of BQ-123 did not exhibit significant vasculoprotection (neointima:media ratio of 128% vehicle control). However, this dosage regimen of BQ-123 was associated with significant and selective ETA receptor antagonism. The systemic pressor response to exogenous ET-1 administration was inhibited by 91% (p < 0.05), whereas the associated depressor response was not different from that observed in vehicle-treated rats. Therefore, since chronic administration of pharmacologic doses of the ETA-selective antagonist BQ-123 does not prevent lesion formation in the RCCA model, whereas the ETA/B receptor antagonist SB 209670 is vasculoprotective, the data implicate a significant role for the ETB receptor subtype, either exclusively or in concert with ETA receptor activation, in the pathogenesis of neointima formation in the rat.