Normalization by edaravone, a free radical scavenger, of irradiation-reduced endothelial nitric oxide synthase expression.
We investigated the therapeutic effect of edaravone, a free radical scavenger, on alterations in endothelium-dependent relaxation and endothelial nitric oxide synthase (eNOS) expression in the rabbit ear central artery at 2 weeks after exposure to a dose of 45 Gy radiation with a cobalt60 unit. For treatment with edaravone, edaravone was given daily to the animals from the day before irradiation at an intrapenetreal dose of 10 mg/kg twice a day. The endothelium-dependent relaxant response to acetylcholine was markedly impaired in irradiated vessels. Edaravone treatment improved the response to the level observed in nonirradiated control vessels. Using immunohistochemical and Western blot techniques, we showed that protein expression of eNOS in irradiated vessels was reduced to about 50% of control and that edaravone treatment returned it nearly to intact levels. Gene expression of eNOS, analyzed by reverse transcription-competitive polymerase chain reaction, was found to be reduced from the control level by 47% following irradiation. The reduced level of eNOS mRNA in irradiated vessels was almost completely normalized by edaravone treatment. These results suggest that edaravone has a protective effect on the reduced expression of eNOS and its associated endothelial cell dysfunction in the vessels following irradiation. We thus assume that oxygen-free radicals may be closely related to the irradiation-induced derangement of the eNOS gene regulation.
Zhang
Xiao-Hong
XH
Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
Matsuda
Naoyuki
N
Jesmin
Subrina
S
Sakuraya
Fumika
F
Gando
Satoshi
S
Kemmotsu
Osamu
O
Hattori
Yuichi
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D015153:Blotting, Western; D004423:Ear / Q000098:blood supply; D000077553:Edaravone; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects*; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000528:radiation effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D012333:RNA, Messenger; D014665:Vasodilator Agents; D010656:Phenylephrine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D000077553:Edaravone; D000983:Antipyrine