Molecular mechanisms of irradiation-induced impairment eNOS expression

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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 central artery at 2 weeks after exposure to a dose of 45 Gy radiation with a cobalt^<60> 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 restored it nearly to intact levels. Gene expression of eNOS, analyzed by RT-PCR, was found to be reduced from the control level by 47% following irradiation. The reduction in eNOS mRNA observed in irradiated vessels was almost completely prevented 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.