Angiotensin converting enzyme inhibitor attenuates oxidative stress-induced endothelial cell apoptosis via p38 MAP kinase inhibition.
BACKGROUND
The effects of angiotensin converting enzyme (ACE) inhibitors on oxidative stress-induced apoptosis of endothelial cells and the intracellular signaling were investigated.


METHODS
Cultured endothelial cells derived from a bovine carotid artery were treated with H2O2 or TNF-alpha to induce apoptosis. Apoptosis was evaluated by DNA fragmentation and cell viability, p38 MAP kinase activity by Western blotting, and oxidative stress by formation of 8-isoprostane. The effects of ACE inhibitors were examined by adding them into the medium throughout the experiments.


RESULTS
Apoptosis was attenuated by ACE inhibitors, temocapril and captopril, in a dose-dependent manner (1-100 micromol/l). H2O2 (0.2 mmol/l for 1.5 h) or TNF-alpha (10 ng/ml for 72 h) treatment stimulated the activities of p38 MAP kinase. Temocapril and captopril decreased the activity of p38 MAP kinase as well as 8-isoprostane formation induced by H2O2. A p38 MAP kinase inhibitor, SB203580, partially inhibited the effect of temocapril on apoptosis.


CONCLUSIONS
These results suggest that ACE inhibitors protect endothelial cells from oxidative stress-induced apoptosis, and that p38 MAP kinase plays a critical role in the process.
Yu
Wei
W
Department of Geriatric Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Akishita
Masahiro
M
Xi
Hang
H
Nagai
Kumiko
K
Sudoh
Noriko
N
Hasegawa
Hiroshi
H
Kozaki
Koichi
K
Toba
Kenji
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D018384:Oxidative Stress; D011725:Pyridines / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D013841:Thiazepines; D014409:Tumor Necrosis Factor-alpha; C055603:temocapril hydrochloride; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580