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-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 B(2) 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.
Desideri
Giovambattista
G
Department of Internal Medicine and Public Health, University of L'Aquila, Piazzale S. Tommasi 1, 67100 Coppito, L'Aquila, Italy.
Grassi
Davide
D
Croce
Giuseppe
G
Bocale
Raffaella
R
Tiberti
Sergio
S
Evangelista
Stefano
S
Necozione
Stefano
S
Di Orio
Ferdinando
F
Ferri
Claudio
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D009566:Nitrates; D009573:Nitrites; D016877:Oxidants; D009569:Nitric Oxide; D005978:Glutathione