Fernandez-Alfonso M S, Martorana P A, Licka I, van Even P, Trobisch D, Schölkens B A, Paul M
Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Hypertension. 1997 Aug;30(2 Pt 1):272-7. doi: 10.1161/01.hyp.30.2.272.
Several studies have demonstrated the effectiveness of angiotensin I-converting enzyme (ACE) inhibitors in preventing the neointima formation found after denudation of the rat carotid artery by balloon injury. The aim of the present study was to determine the role of ACE in this model and to compare the treatment with the ACE inhibitor ramiprilat with that with the angiotensin II antagonist HR 720. The endothelial layer of the left carotid artery was removed using an inflated balloon catheter. Injured and control vessels were both submitted to histomorphological analysis and DNA content quantification at 2, 4, 6, 8, 12, and 14 days after injury. Evaluation of neointima thickening demonstrated a slow but steady increase of neointima that was significant after day 6 and reached 30% of the lumen in 2 weeks. This was paralleled by an increase in DNA content, which was significant 4 days after injury. ACE mRNA levels were quantified by polymerase chain reaction after reverse transcription. Measurement of ACE mRNA levels revealed a significant upregulation 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. ACE activity was also significantly enhanced at 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. In addition, the treatment with ramiprilat was more efficient in reducing neointima formation than that with HR 720. These data underlie the role of ACE in this model of restenosis. The early induction of ACE expression after endothelial injury but before significant changes in the vessel structure suggests that ACE activity might be one of the mechanisms that trigger neointima formation in the rat.
多项研究已证明血管紧张素I转换酶（ACE）抑制剂在预防大鼠颈动脉球囊损伤剥脱后出现的新生内膜形成方面的有效性。本研究的目的是确定ACE在该模型中的作用，并比较ACE抑制剂雷米普利拉与血管紧张素II拮抗剂HR 720的治疗效果。使用充气球囊导管去除左颈动脉的内皮。在损伤后2、4、6、8、12和14天，对损伤血管和对照血管都进行组织形态学分析和DNA含量定量。新生内膜增厚评估显示，新生内膜缓慢但持续增加，在第6天后显著增加，2周内达到管腔的30%。这与DNA含量的增加平行，DNA含量在损伤后4天显著增加。通过逆转录后的聚合酶链反应对ACE mRNA水平进行定量。ACE mRNA水平的测量显示，损伤后2天和8天有显著上调，与后期时间点的对照组织相比无显著差异。损伤后2天和8天ACE活性也显著增强，与后期时间点的对照组织相比无显著差异。此外，雷米普利拉治疗在减少新生内膜形成方面比HR 720更有效。这些数据说明了ACE在该再狭窄模型中的作用。内皮损伤后但在血管结构发生显著变化之前ACE表达的早期诱导表明，ACE活性可能是触发大鼠新生内膜形成的机制之一。
