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Vitamin C Prevents Radiation‐Induced Endothelium‐Dependent Vasomotor Dysfunction And De‐Endothelialization By Inhibiting Oxidative Damage In The Rat
Author(s) -
On YoungKeun,
Kim HyoSoo,
Kim SeokYeon,
Chae InHo,
Oh ByungHee,
Lee MyoungMook,
Park YoungBae,
Choi YunShik,
Chung MyungHee
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03528.x
Subject(s) - chemistry , vitamin c , endocrinology , medicine , nitric oxide , endothelium , vitamin , von willebrand factor , endothelial dysfunction , acetylcholine , vitamin d and neurology , vasodilation , oxidative stress , malondialdehyde , platelet
SUMMARY 1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation‐induced damage of the endothelium. 2. Female Sprague‐Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137 Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8‐hydroxydeoxyguanosine (OH‐dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine‐induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L ‐NAME (100 μ g/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH‐dG in the aorta (1.02 ± 0.27 vs 2.61 ± 0.78 OH‐dG/10 5 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 ± 0.23 OH‐dG/10 5 dG; P < 0.01). Irradiation caused significant de‐endothelialization (von Willebrand factor (vWF) staining was 93 ± 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 ± 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial‐dependent vasodilation that could be prevented by vitamin C, partly through anti‐oxidant mechanisms.