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

Angiotensin converting enzyme inhibitors (ACE-1) are able to reduce the formation of the potent vasoconstrictor endothe!in-l and increase nitric oxide bioavailability in human vascular endothelial cells (HUVECs). We tested the effects of two sulfhydrylcontaining A(;:F-I,7.ofenoprilat, and captopril, and two nonsulthydryl containing ACE-I, enalaprilat and tisinopril, on endothelinl/ nitiic oxide balance and oxidative stress in HUVHCs. Alt the four tested ACE-1 reduced endothelin-1 secretion and increased nitric oxide metabolite production by HUVEC^s. 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. Theeffect of ACE-I on endothelin-l and nitric oxide metabolite production is mediated by the activation of bradykinin B; receptor being counteracted, at least in part, by a specific antagonist. Zofenoprilat and, to a lesser extent, captopril also reduced oxidative stress in HUVEC^s. In conclusion, among the four tested ACE'l, zofenoprilat was more effective in improving endothelin-1/nitric oxide balance in HUVECs likely because of its greater antioxidant properties.