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英文论文.pdfVIP

Hindawi Publishing Corporation Mediators of Inflammation Volume 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 1 Department of Internal Medicine and Public Health, University of L’Aquila, Piazzale S. Tommasi 1, 67100 Coppito, L’Aquila, Italy 2 Preclinical Development Department, Menarini Ricerche S.p.A, Via Sette Santi 1, 50131 Firenze, Italy Correspondence should be addressed to Stefano Evangelista, sevangelista@menarini-ricerche.it Received 15 July 2008; Accepted 22 September 2008 Recommended by Jan van Amsterdam 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%