Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril.
Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril.
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DOI：
10.1111/j.1440-1843.2012.02247.x
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Medhora MM
中科院分区：
文献类型：
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作者：
Molthen RC;Wu Q;Fish BL;Moulder JE;Jacobs ER;Medhora MM
大鼠胸部单次10Gy射线照射后2个月，肺血管紧张素转换酶(ACE)活性、肺血管扩张性和远端血管密度降低，肺血管阻力(PVR)增加。在这项研究中，我们评估了肾素-血管紧张素系统(RAS)调节剂，ACE抑制剂卡托普利，以减轻这种肺血管损伤的潜力。照射后2个月，观察大鼠放射性肺炎的发生发展过程。大鼠在辐射暴露后立即或2周后，用2剂ACE抑制剂卡托普利溶解在他们的饮用水中进行治疗。为了确定肺血管反应，我们测量了肺血流动力学、肺血管紧张素转换酶活性、肺动脉扩张性和外周血管密度。卡托普利以血管活性给药，但不是较低剂量，可减轻辐射引起的肺血管损伤。更重要的是，即使在暴露后推迟两周进行药物治疗，也能观察到这些有益的效果。卡托普利减少了肺血管损伤，这支持在发生意外的辐射事件(如核事故)后将其用作放射增强剂。
A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident.