Protective effects of sulfhydryl-containing angiotensin converting enzyme inhibitors against free radical injury in endothelial cells.
The effects of SH-containing (captopril, epi-captopril, and the free-SH form of zofenopril) and non-SH-containing (enalaprilat and lisinopril) angiotension converting enzyme (ACE) inhibitors on free radical injury in cultured endothelial cells were studied. When cultured endothelial cells were exposed to a superoxide and hydroxyl radical generating system (dihydroxyfumarate + Fe3(+)-ADP) for 30 min, lipid peroxidation [malondialdehyde (MDA) formation] occurred, and cellular viability (trypan blue exclusion) decreased to 41%; concomitantly, plasma membrane blebbing, assessed by scanning electron microscopy, occurred in 65% of the cells. Preincubation of the cells with each of the SH-agents before free radical addition resulted in an equipotent concentration-dependent (10-200 microM) inhibition (15-60%) of MDA formation; both losses in cellular viability and percent blebbed cells were reduced significantly (P less than 0.05) by concentrations as low as 10 microM of each SH-agent. However, neither of the non-SH agents up to 200 microM produced any major effect. When the effects on hydroxyl radical formation in the system were assessed by ESR spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), concentrations of 10 and 50 microM of the SH-agents reduced the intensity of the DMPO-OH adducts 20 and 50% respectively. Similar results were observed when the hydroxyl radical was generated from the Fenton-reagents (Fe2+ + H2O2), suggesting direct hydroxyl radical scavenging. Thus, these results demonstrate that the SH-containing ACE agents are capable of protecting the endothelial cells against free radical induced lipid peroxidation and cell injury; the mechanism may be due to direct hydroxyl radical scavenging.
Mak
I T
IT
Department of Physiology, George Washington University Medical Center, Washington, DC 20037.
Freedman
A M
AM
Dickens
B F
BF
Weglicki
W B
WB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers; D015227:Lipid Peroxidation / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds