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 5×10^-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 (Pramipril≫quinapril=trandolapril= enalapril, with significant differences between perindopril and quinapril (P