Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Radiat Res. 2011 Oct;176(4):474-85. doi: 10.1667/rr2598.1. Epub 2011 Jul 25.
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.
电离辐射已被牵连到重大心血管并发症的发展中。由于辐射暴露与太空探索有关，宇航员患加速心血管疾病的风险可能会增加。本研究以太空辐射模型，调查了高原子序数、高能（HZE）铁离子辐射对血管和内皮功能的影响。大鼠接受单次全身铁离子辐射剂量为 0、0.5 或 1Gy。暴露后 6 和 8 个月测量体内主动脉僵硬和体外主动脉张力反应，作为慢性血管损伤的指标。接受 1Gy 铁离子照射的大鼠表现出明显的主动脉僵硬增加，如脉搏波速度测量所示。来自受照射大鼠的主动脉环显示出内皮依赖性松弛受损，这与内皮功能障碍一致。急性黄嘌呤氧化酶（XO）抑制或活性氧（ROS）清除可使内皮依赖性反应恢复正常。此外，全身照射后 4 个月，大鼠主动脉中 XO 活性显著升高。此外，辐射后立即开始并持续到安乐死的 XO 抑制完全抑制了辐射依赖性 XO 激活。1Gy 照射后 ROS 产生增加，而一氧化氮（NO）的产生显著受损。XO 抑制恢复了 NO 和 ROS 的产生。最后，膳食 XO 抑制在辐射暴露后维持了正常的内皮功能和血管僵硬。这些结果表明，辐射诱导了 XO 依赖性 ROS 产生和硝基-氧化还原失衡，导致慢性血管功能障碍。因此，XO 是放射防护的潜在靶点。增强对血管辐射损伤的理解可能导致开发有效方法来改善辐射引起的血管损伤。
