Differences in the effect of angiotensin-converting enzyme inhibitors on the rate of endothelial cell apoptosis: in vitro and in vivo studies

Aim: 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.

Methods: 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).

Results: 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.

Conclusion: Our experiments suggest differences between ACE inhibitors in terms of inhibition of endothelial Apoptosis in vivo.