Mediators of Inflammation
Volume 2008 (2008), Article ID 305087, 7 pages
doi:10.1155/2008/305087
Research Article

Different Effects of Angiotensin Converting Enzyme Inhibitors on Endothelin-1 and Nitric Oxide Balance in Human Vascular Endothelial Cells: Evidence of an Oxidant-Sensitive Pathway

Giovambattista Desideri,1 Davide Grassi,1 Giuseppe Croce,1 Raffaella Bocale,1 Sergio Tiberti,1 Stefano Evangelista,2 Stefano Necozione,1 Ferdinando Di Orio,1 and Claudio Ferri1

1Department of Internal Medicine and Public Health, University of L'Aquila, Piazzale S. Tommasi 1, 67100 Coppito, L'Aquila, Italy
2Preclinical Development Department, Menarini Ricerche S.p.A, Via Sette Santi 1, 50131 Firenze, Italy

Received 15 July 2008; Accepted 22 September 2008

Academic Editor: Jan van Amsterdam

Copyright © 2008 Giovambattista Desideri et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Angiotensin converting enzyme inhibitors (ACE-I) are able to reduce the formation of the potent vasoconstrictor endothelin-1 and increase nitric oxide bioavailability in human vascular endothelial cells (HUVECs). We tested the effects of two sulfhydryl containing ACE-I, zofenoprilat, and captopril, and two nonsulfhydryl containing ACE-I, enalaprilat and lisinopril, on endothelin-1/nitric oxide balance and oxidative stress in HUVECs. All the four tested ACE-I reduced endothelin-1 secretion and increased nitric oxide metabolite production by HUVECs. However, zofenoprilat (−42% after 8 hours of incubation) was more effective (P<.05) than enalaprilat (−25%), lisinopril (−21%), and captopril (−30%) in reducing endothelin-1 secretion. Similarly, zofenoprilat (+110% after 8 hours of incubation) was more effective (P<.05) than enalaprilat (+64%), lisinopril (+63%), and captopril (+65%) in increasing nitric oxide metabolite production. The effect of ACE-I on endothelin-1 and nitric oxide metabolite production is mediated by the activation of bradykinin B2 receptor being counteracted, at least in part, by a specific antagonist. Zofenoprilat and, to a lesser extent, captopril also reduced oxidative stress in HUVECs. In conclusion, among the four tested ACE-I, zofenoprilat was more effective in improving endothelin-1/nitric oxide balance in HUVECs likely because of its greater antioxidant properties.