Warfield M E, Schneidkraut M J, Ramwell P W, Kot P A
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007.
Radiat Res. 1990 Jan;121(1):63-6.
Previous studies showed that 20 Gy whole-body gamma irradiation results in a decreased response of the abdominal aorta to the stable thromboxane A2 (TXA2) mimic, U46619. The present study evaluated the effect of WR2721 on this radiation-induced decrease in vascular responsiveness. Rats receiving WR2721 (200 mg/kg, i.p.) 20 min before irradiation showed no depression in vascular reactivity to U46619 compared to control. The abolition of the radiation-induced decrease in vascular responsiveness was not caused by a direct vasoconstrictor action of WR2721 or its metabolites. The vascular response of rat abdominal aortic rings to KCl was unchanged after in vivo exposure to ionizing radiation. WR2721 did not alter the vascular response to KCl. These studies confirm that exposure to whole-body ionizing radiation decreased abdominal aortic vascular responsiveness to U46619. This depressed vascular reactivity can be abolished by pretreatment with the radioprotectant, WR2721. These observations may provide a rapid initial screening method for evaluating the in vivo efficacy of radioprotectant drugs.
先前的研究表明，20 Gy全身γ射线照射会导致腹主动脉对稳定的血栓素A2（TXA2）类似物U46619的反应性降低。本研究评估了WR2721对这种辐射诱导的血管反应性降低的影响。与对照组相比，在照射前20分钟接受WR2721（200 mg/kg，腹腔注射）的大鼠对U46619的血管反应性没有降低。辐射诱导的血管反应性降低的消除不是由WR2721或其代谢产物的直接血管收缩作用引起的。体内暴露于电离辐射后，大鼠腹主动脉环对氯化钾的血管反应没有改变。WR2721没有改变对氯化钾的血管反应。这些研究证实，全身电离辐射暴露会降低腹主动脉对U46619的血管反应性。这种降低的血管反应性可以通过用辐射防护剂WR2721预处理来消除。这些观察结果可能为评估辐射防护药物的体内疗效提供一种快速的初步筛选方法。
