Capasso G, Anastasio P, Giordano D, Albarano L, De Santo N G
Am J Nephrol. 1987;7(3):228-34. doi: 10.1159/000167470.
The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.
有机金属顺铂具有强大的抗肿瘤特性。然而，其使用有时会因显著的肾毒性而变得复杂。这表现为肾小管坏死和肾小球滤过率（GFR）受损。另一方面，已证明心房利钠因子（ANF）可增加正常血容量正常的大鼠的GFR。因此，在本研究中，我们测试了这种新的强效利钠化合物是否能恢复一些受顺铂影响的肾脏参数。为了研究这个问题，通过腹腔注射10mg/kg体重（b.w.）的顺铂在9只大鼠中诱导急性肾衰竭。72小时后使用3H-菊粉清除法研究肾功能，并与5只正常血容量正常的大鼠的肾功能进行比较。经顺铂处理的大鼠显示出血尿素氮水平升高、全肾GFR降低74%（0.308±0.047对1.17±0.08ml/min/100g b.w.）以及尿、钠和钾的分数排泄显著增加。在进行2次对照清除后，将合成ANF以首剂（12μg/kg b.w.）静脉注射，然后以恒定输注（1μg/kg/min）给予6只经顺铂处理的大鼠。这迅速使GFR翻倍（0.603±0.113ml/min/100g b.w.），并导致尿、钠和钾的排泄率显著增加。这些结果表明，给予ANF对顺铂诱导的急性肾衰竭实验模型具有有益作用。
