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Functional and morphological damage of endothelium in rabbit ear artery following irradiation with cobalt 60
Author(s) -
Qi Fazhi,
Sugihara Tsuneki,
Hattori Yuichi,
Yamamoto Yuhei,
Kanno Morio,
Abe Kazuhiro
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701654
Subject(s) - endothelium , enos , sodium nitroprusside , superoxide dismutase , nitric oxide synthase , endothelial stem cell , nitric oxide , endothelial dysfunction , medicine , acetylcholine , endocrinology , endothelial nos , chemistry , biology , biochemistry , oxidative stress , in vitro
The relaxant actions of acetylcholine and A23187 were examined in the rabbit central ear artery at different intervals following exposure to different doses of radiation with a cobalt 60 unit. The artery was irradiated with a dose of 10 Gy, 20 Gy and 45 Gy. Radiation caused dose‐ and time‐dependent impairment of the endothelium‐dependent relaxations. The impaired endothelium‐dependent relaxations occurred as early as 1 week postirradiation and persisted throughout the experimental period (10 weeks). The endothelium‐independent response to sodium nitroprusside was well preserved up to 6 weeks after irradiation. The contractile response to noradrenaline was unaltered by irradiation throughout the experimental period, but in contrast to control vessels, an increase in the sensitivity to noradrenaline in the presence of the nitric oxide synthase (NOS) inhibitor N G ‐nitro‐ L ‐arginine was not observed in the irradiated vessels. The impaired endothelium‐dependent relaxations in the irradiated vessels were not improved by pretreatment with the NOS substrate L ‐arginine, the cyclo‐oxygenase inhibitor indomethacin or the free radical scavengers superoxide dismutase and catalase. Scanning electron microscopy indicated morphologically intact endothelial cells within the first 4 weeks after irradiation. Western blot analysis showed a significant decrease in the expression of endothelial NOS (eNOS) in the irradiated vessels. These data indicate that endothelial cell function is specifically impaired in the irradiated vessels before morphological endothelial cell damage can be detected. This impairment may be related to diminished eNOS expression.British Journal of Pharmacology (1998) 123 , 653–660; doi: 10.1038/sj.bjp.0701654