Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors
Suppression of experimental abdominal aortic aneurysms in the rat by treatment with angiotensin-converting enzyme inhibitors
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DOI：
10.1067/mva.2001.112810
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发表时间：
2001-05-01
影响因子：
4.3
通讯作者：
Thompson, RW
中科院分区：
文献类型：
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作者：
Liao, SX;Miralles, M;Thompson, RW
目的：细胞外基质的病理性重塑是腹主动脉瘤（AAA）发生和发展的关键机制。虽然已知血管紧张素转换酶（ACE）抑制剂可在其他条件下改变血管壁重塑，但其对AkAs的影响尚不清楚。在这项研究中，我们评估的效果ACE抑制剂在啮齿动物模型的动脉瘤development.Methods：雄性Wistar大鼠进行短暂的主动脉灌注与猪胰弹性蛋白酶，其次是治疗与三个ACE抑制剂（卡托普利[CP]，赖诺普利[LP]，或依那普利[Er]），血管紧张素（AT）（1）受体拮抗剂（氯沙坦[LOS]），或水单独（每组9只大鼠）。在弹性蛋白酶灌注前和第14天测量血压和主动脉直径（AD），AAA定义为AD（Δ AD）增加超过100%。主动脉壁的结构特征进行了检查，通过光学microscope.Results：动脉瘤扩张一贯开发14天内的弹性蛋白酶灌注在未经处理的大鼠，符合发展的透壁炎症反应和破坏的弹性介质（平均Δ AD，223% +/- 28%）。三种ACE抑制剂预防AAA发展（平均Δ AD：CP，67% +/- 4%; LP，18% +/- 12%;和EP，14% +/- 3%;每个P <0.05与对照组相比）。ACE抑制剂也减弱了中膜弹性蛋白的降解，而不减少炎症反应。令人惊讶的是，血管紧张素转换酶抑制剂的血管紧张素转换酶抑制作用与其对全身血液动力学的影响无关，LOS与未治疗的对照组相比对动脉瘤的发展没有显着影响（平均Δ AD，186% +/-19%hCLUSION：用血管紧张素转换酶抑制剂治疗抑制了大鼠弹性蛋白酶诱导的AAA的发展。虽然这与内侧弹性蛋白的保存有关，但这些作用的机制似乎与单独的血流动力学改变或仅由AT（1）受体介导的事件不同。ACE抑制剂如何影响主动脉壁基质重塑尚需进一步研究。
Purpose: Pathologic remodeling of the extracellular matrix is a critical mechanism in the development and progression of abdominal aortic aneurysms (AAAs). Although angiotensin-converting enzyme (ACE) inhibitors are known to alter vascular wall remodeling in other conditions, their effects on AkAs are unknown. In this study we assessed the effect of ACE inhibitors in a rodent model of aneurysm development.Methods: Male Wistar rats underwent transient aortic perfusion with porcine pancreatic elastase, followed by treatment with one of three ACE inhibitors (captopril [CP], lisinopril [LP], or enalapril [Er]), an angiotensin (AT)(1) receptor antagonist (losartan [LOS]), or water alone (9 rats in each group). Blood pressure and aortic diameter (AD) were measured before elastase perfusion and on day 14, with an AAA defined as an increase in AD (Delta AD) of more than 100%. The structural features of the aortic wall were examined by means of light microscopy.Results: Aneurysmal dilatation consistently developed within 14 days of elastase perfusion in untreated rats, coinciding with the development of a transmural inflammatory response and destruction of the elastic media (mean Delta AD, 223% +/- 28%). Ah three ACE inhibitors prevented AAA development (mean Delta AD: CP, 67% +/- 4%; LP, 18% +/- 12%; and EP, 14% +/- 3%; each P < .05 vs controls). ACE inhibitors also attenuated the degradation of medial elastin without diminishing the inflammatory response. Surprisingly, the aneurysm-suppressing effects of ACE inhibitors were dissociated from their effects on systemic hemodynamics, and LOS had no significant effect on aneurysm development compared with untreated controls (mean Delta AD, 186% +/- 19%).Conclusion: Treatment with ACE inhibitors suppresses the development of elastase-induced AAAs in the rat. Although this is associated with the preservation of medial elastin, the mechanisms underlying these effects appear to be distinct from hemodynamic alterations alone or events mediated solely by AT(1) receptors. Further studies are needed to elucidate how ACE inhibitors influence aortic wall matrix remodeling during aneurysmal degeneration.