Cohen Eric P, Fish Brian L, Sharma Mukut, Li X Allen, Moulder John E
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Transl Res. 2007 Aug;150(2):106-15. doi: 10.1016/j.trsl.2007.03.004. Epub 2007 May 25.
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(1) 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(1) receptors. The effect of AT(2) blockade in radiation nephropathy cannot be explained by binding to the AT(1) receptor, and the efficacy of the AT(1) blockade in the same model cannot be explained by unopposed overstimulation of the AT(2) receptor.
实验研究表明，阻断血管紧张素II 1型（AT(1)）受体对减轻和治疗辐射诱导的慢性肾衰竭有效。此外，用PD - 123319阻断血管紧张素II 2型（AT(2)）受体在实验性放射性肾病中也有适度但可重复的有益作用，并且可能增强AT(1)受体阻滞剂（L - 158,809）的疗效。那些研究无法排除AT(2)受体阻断作用是非特异性的可能性。当前的研究证实了AT(2)受体阻断对减轻实验性放射性肾病的疗效，但自相矛盾的是在肾膜中未检测到AT(2)受体结合水平。然而，生物测定结果显示，AT(2)受体阻滞剂的循环水平低几个数量级，无法阻断AT(1)受体。辐射性肾病中AT(2)受体阻断的作用不能用与AT(1)受体结合来解释，并且同一模型中AT(1)受体阻断的疗效也不能用AT(2)受体无对抗的过度刺激来解释。
