Ceconi C, Francolini G, Bastianon D, Gitti G L, Comini L, Ferrari R
Department of Cardiology, University of Ferrara, Corso Giovecca 203, 44100, Ferrara, Italy.
Cardiovasc Drugs Ther. 2007 Dec;21(6):423-9. doi: 10.1007/s10557-007-6068-5. Epub 2007 Nov 15.
An imbalance between endothelial apoptosis and regeneration is one of the initiating events in atherosclerosis. Angiotensin-converting enzyme (ACE) inhibition corrects the endothelial dysfunction observed in coronary artery disease, and this could be the consequence of a reduction in the rate of endothelial apoptosis. The aim of this study was to investigate the effect of different ACE inhibitors on endothelial apoptosis.
We examined the effect of five ACE inhibitors (enalapril, perindopril, quinapril, ramipril, and trandolapril) on the rate of endothelial apoptosis, either in vitro in human umbilical vein endothelial cells (HUVECs), using a serum deprivation method to induce apoptosis, or in vivo in rats, inducing apoptosis via endotoxic shock with Escherichia coli lipopolysaccharides (LPS).
We were unable to detect any significant effect of ACE inhibition on the rate of in vitro endothelial apoptosis at concentrations ranging from 5 x 10(-8) to 10(-6) M. In contrast, chronic in vivo administration of ACE inhibitors to rats at dosages that had similar hypotensive effects reduced the rate of LPS-induced apoptosis significantly for perindopril (P < 0.001) and nonsignificantly for the other ACE inhibitors. The order of potency of the ACE inhibitors tested was perindopril > ramipril >> quinapril = trandolapril = enalapril, with significant differences between perindopril and quinapril (P < 0.01), trandolapril (P < 0.001), and enalapril (P < 0.001). The difference between perindopril and ramipril did not reach significance.
Our experiments suggest differences between ACE inhibitors in terms of inhibition of endothelial apoptosis in vivo.
内皮细胞凋亡与再生之间的失衡是动脉粥样硬化的起始事件之一。血管紧张素转换酶（ACE）抑制可纠正冠心病中观察到的内皮功能障碍，这可能是内皮细胞凋亡率降低的结果。本研究的目的是探讨不同ACE抑制剂对内皮细胞凋亡的影响。
我们研究了五种ACE抑制剂（依那普利、培哚普利、喹那普利、雷米普利和群多普利）对内皮细胞凋亡率的影响，体外实验使用人脐静脉内皮细胞（HUVECs），采用血清剥夺法诱导凋亡；体内实验使用大鼠，通过大肠杆菌脂多糖（LPS）内毒素休克诱导凋亡。
在5×10⁻⁸至10⁻⁶M的浓度范围内，我们未检测到ACE抑制对体外内皮细胞凋亡率有任何显著影响。相比之下，以具有相似降压效果的剂量对大鼠进行ACE抑制剂的慢性体内给药，培哚普利可显著降低LPS诱导的凋亡率（P < 0.001），其他ACE抑制剂则无显著降低。所测试的ACE抑制剂的效力顺序为培哚普利>雷米普利>>喹那普利 =群多普利 =依那普利，培哚普利与喹那普利（P < 0.01）、群多普利（P < 0.001）和依那普利（P < 0.001）之间存在显著差异。培哚普利与雷米普利之间的差异未达到显著水平。
我们的实验表明，ACE抑制剂在体内抑制内皮细胞凋亡方面存在差异。
