Goor Y, Peer G, Iaina A, Blum M, Wollman Y, Chernihovsky T, Silverberg D, Cabili S
Department of Internal Medicine, Tel Aviv Medical Center, Israel.
Diabetologia. 1996 Sep;39(9):1036-40. doi: 10.1007/BF00400651.
Changes in nitric oxide (NO) levels were determined in ischaemic acute renal failure in streptozotocin-induced diabetes mellitus rats. Two weeks after streptozotocin administration and immediately after right nephrectomy, the left renal artery was occluded for 60 min. Similar procedures were carried out in non-diabetic rats. The nitrite (NO2) + nitrate (NO3) levels were measured in plasma and urine. The effects of chronic oral supplementation with L-arginine and an NO synthase inhibitor (N-omega-nitro-L-arginine) were also studied in both diabetic and non-diabetic rats before and after renal artery clamping. The rats with diabetic acute renal failure had a much lower creatinine clearance (90 +/- 22 microliters.min-1. 100g body weight-1, p < 0.005), and higher fractional excretion of sodium (FENa)% (10.90 +/- 4.2, p < 0.001) and protein excretion (2078 +/- 69 micrograms/ml creatinine clearance, p < 0.001) compared with the respective values in the non-diabetic groups (163 +/- 30; 1.46 +/- 86; 453.3 +/- 31). The plasma and urine NO2 + NO3 levels were significantly higher in the untreated diabetic rats compared with the untreated normal rats before ischaemia (p < 0.001). The ischaemic acute renal failure in non-diabetic rats increased the plasma and urinary NO2 + NO3 excretion after ischaemia. The urinary excretion of these metabolites decreased significantly and their plasma levels remained unchanged in the ischaemic diabetic rats. The L-arginine administration resulted in a small but significantly higher creatinine clearance after clamping in the non-diabetic rats. The NO synthase inhibitor caused deterioration in renal function in all ischaemic and non-ischaemic groups. In summary, the greater vulnerability to ischaemia of the diabetic kidney seems to be associated with both impaired response to and impaired production of NO.
在链脲佐菌素诱导的糖尿病大鼠缺血性急性肾衰竭模型中，检测一氧化氮（NO）水平的变化。给予链脲佐菌素两周后并在右肾切除术后立即将左肾动脉闭塞60分钟。对非糖尿病大鼠进行类似操作。测定血浆和尿液中亚硝酸盐（NO2）+硝酸盐（NO3）水平。在肾动脉夹闭前后，还研究了慢性口服补充L-精氨酸和一氧化氮合酶抑制剂（N-ω-硝基-L-精氨酸）对糖尿病和非糖尿病大鼠的影响。与非糖尿病组（163±30；1.46±86；453.3±31）的相应值相比，糖尿病急性肾衰竭大鼠的肌酐清除率显著降低（90±22微升·分钟-1·100克体重-1，p<0.005），钠分数排泄率（FENa）%显著升高（10.90±4.2，p<0.001），蛋白质排泄量显著升高（2078±69微克/毫升肌酐清除率，p<0.001）。与缺血前未治疗的正常大鼠相比，未治疗的糖尿病大鼠血浆和尿液中NO2+NO3水平显著升高（p<0.001）。非糖尿病大鼠缺血性急性肾衰竭导致缺血后血浆和尿液中NO2+NO3排泄增加。缺血性糖尿病大鼠这些代谢产物的尿液排泄显著减少，而血浆水平保持不变。给予L-精氨酸后，非糖尿病大鼠夹闭后肌酐清除率虽有小幅升高但显著高于未给药组。一氧化氮合酶抑制剂使所有缺血和非缺血组的肾功能恶化。总之，糖尿病肾脏对缺血的易感性增加似乎与对NO的反应受损和NO生成受损均有关。
