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

Abstract EN

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.