Ito Keiichi, Chen Jie, Vaughan E Darracott, Seshan Surya V, Poppas Dix P, Felsen Diane
Department of Urology, New York Presbyterian Children's Hospital, New York, USA.
J Urol. 2004 Feb;171(2 Pt 1):926-30. doi: 10.1097/01.ju.0000105073.67242.eb.
Unilateral ureteral obstruction (UUO) results in a significant change in renal blood flow (RBF) and glomerular filtration rate (GFR) by 24 hours. The intake of L-arginine, a substrate of nitric oxide (NO) synthase (NOS), can augment NO production. NO can maintain renal function through its vasodilatory action. Therefore, we examined the effect of dietary arginine supplementation on renal function in UUO.
GFR and RBF were measured by inulin and para-aminohippurate clearance, respectively, in control rats and in rats 24 hours after UUO. Rats were given arginine with or without the concomitant administration of N-nitro-L-arginine methyl ester. Urinary nitrate/nitrite (NO2/NO3) was measured by the Griess reaction and urinary cyclic guanosine monophosphate was determined by enzyme-linked immunosorbent assay. The expression of renal inducible NOS was determined by immunohistochemistry.
Urinary NO2/NO3 was significantly increased after 2 weeks of arginine, confirming increased NO production. In control rats GFR and RBF were not significantly different in untreated vs arginine treated groups. In contrast, arginine treatment significantly increased GFR in the obstructed kidney (0.06 +/- 0.01 to 0.14 +/- 0.02 ml per minute per 100 gm) and the contralateral kidney compared with control UUO. RBF was also significantly increased by arginine. The increases in renal function with arginine were blunted by a NOS inhibitor in obstructed and contralateral kidneys. Inducible NOS expression was increased in obstructed and contralateral kidneys.
This study demonstrates that L-arginine supplementation can improve renal function in acute UUO. This finding suggests that NO system may be a future site of pharmacological intervention for UUO.
单侧输尿管梗阻（UUO）在24小时内会导致肾血流量（RBF）和肾小球滤过率（GFR）发生显著变化。一氧化氮（NO）合酶（NOS）的底物L-精氨酸的摄入可增加NO的生成。NO可通过其血管舒张作用维持肾功能。因此，我们研究了饮食中补充精氨酸对UUO大鼠肾功能的影响。
分别通过菊粉和对氨基马尿酸清除率测定对照组大鼠和UUO术后24小时大鼠的GFR和RBF。给大鼠给予精氨酸，同时或不同时给予N-硝基-L-精氨酸甲酯。通过格里斯反应测定尿硝酸盐/亚硝酸盐（NO2/NO3），并通过酶联免疫吸附测定法测定尿环磷酸鸟苷。通过免疫组织化学法测定肾诱导型NOS的表达。
精氨酸给药2周后，尿NO2/NO3显著增加，证实NO生成增加。在对照组大鼠中，未治疗组与精氨酸治疗组的GFR和RBF无显著差异。相比之下，与对照UUO组相比，精氨酸治疗显著增加了梗阻肾（从每分钟每100克0.06±0.01增加到0.14±0.02毫升）和对侧肾的GFR。精氨酸也显著增加了RBF。在梗阻肾和对侧肾中，NOS抑制剂减弱了精氨酸对肾功能的改善作用。梗阻肾和对侧肾中诱导型NOS表达增加。
本研究表明，补充L-精氨酸可改善急性UUO大鼠的肾功能。这一发现提示NO系统可能是未来UUO药物干预的靶点。
