Role of the angiotensin II type-2 receptor in radiation nephropathy
Role of the angiotensin II type-2 receptor in radiation nephropathy
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DOI：
10.1016/j.trsl.2007.03.004
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发表时间：
2007-08-01
影响因子：
7.8
通讯作者：
Moulder, John E.
中科院分区：
文献类型：
--
作者：
Cohen, Eric P.;Fish, Brian L.;Moulder, John E.
实验研究表明，阻断血管紧张素II型- 1 （AT(1)）受体可有效缓解和治疗放射引起的慢性肾功能衰竭。此外，PD- 123319阻断血管紧张素II 2型（AT(2)）受体在实验性放射肾病中也有适度但可重复的有益效果，并且可能增强AT阻滞剂（L- 158,809）的疗效。这些研究不能排除阻断AT(2)的作用是非特异性的可能性。目前的研究证实了AT(2)阻断剂对减轻实验性放射肾病的有效性，但矛盾的是，在肾膜中没有检测到AT(2)受体结合水平。然而，生物测定的结果显示，AT(2)阻滞剂的循环水平是数量级太低，无法阻断AT受体。AT(2)阻断在放射性肾病中的作用不能通过与AT、受体的结合来解释，在同一模型中，AT(2)受体的无对抗过度刺激不能解释AT(2)阻断的有效性。
Experimental studies have shown that blockade of the angiotensin II type- 1 (AT(1)) receptor is effective in the mitigation and treatment of radiation -induced chronic renal failure. Also, blockade of the angiotensin II type-2 (AT(2)) receptor with PD- 123319 also had a modest, but reproducible, beneficial effect in experimental radiation nephropathy, and it might augment the efficacy of an AT, blocker (L- 158,809). Those studies could not exclude the possibility that the effects of AT(2) blockade were nonspecific. The current studies confirm the efficacy of AT(2) blockade for mitigation of experimental radiation nephropathy but paradoxically find no detectable level of AT(2) receptor binding in renal membranes. However, the results of a bioassay showed that the circulating levels of the AT(2) blocker were orders-of -magnitude too low to block AT, receptors. The effect of AT(2) blockade in radiation nephropathy cannot be explained by binding to the AT, receptor, and the efficacy of the AT, blockade in the same model cannot be explained by unopposed overstimulation of the AT(2) receptor.