Translator Disclaimer
25 July 2011 HZE 56Fe-Ion Irradiation Induces Endothelial Dysfunction in Rat Aorta: Role of Xanthine Oxidase
Kevin G. Soucy, Hyun Kyo Lim, Jae Hyung Kim, Young Oh, David O. Attarzadeh, Baris Sevinc, Maggie M. Kuo, Artin A. Shoukas, Marcelo E. Vazquez, Dan E. Berkowitz
Author Affiliations +
Abstract

Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage.

by Radiation Research Society
Kevin G. Soucy, Hyun Kyo Lim, Jae Hyung Kim, Young Oh, David O. Attarzadeh, Baris Sevinc, Maggie M. Kuo, Artin A. Shoukas, Marcelo E. Vazquez, and Dan E. Berkowitz "HZE 56Fe-Ion Irradiation Induces Endothelial Dysfunction in Rat Aorta: Role of Xanthine Oxidase," Radiation Research 176(4), 474-485, (25 July 2011). https://doi.org/10.1667/RR2598.1
Received: 16 February 2011; Accepted: 1 June 2011; Published: 25 July 2011
JOURNAL ARTICLE
12 PAGES


Share
SHARE
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top