AIM： To test the hypothesis that locally produced renalendothelin(ET) and nitric oxide(NO) play more important role in initiating proteinuria than circulating ET and NO. METHODS: (1) Rat nephrotic syndrome model was made by single injection of adriamycin, and the urinary protein excretion per 24 hours for every two days was measured. (2) Rat plasma and renal cortex were collected respectively 4 days, 8 days, 32 days and 56 days after the injection, and renal cortex homogenate was further prepared; ET of both plasma and renal cortex homogenate were determined by radioimmunoassay; NO of both plasma and renal homogenate were measured by the method of Griess. (3) The correlation between urinary protein and ET or NO concentration was analyzed respectively. RESULTS: (1) The urinary protein excretion of normal rat was 4-7 mg/d, that in nephrotic rat at the 4 time points was 5, 10, 241 and 201 mg/d, there was a significant increase of that at day 8, peaked at day 32, and less decrease at day 56. (2) The plasma ET in nephrotic rats of the 4 time points was 134, 150, 538 and 445 μg/L, respectively, which of day 8, day 32 and day 56 shown significant higher than that of normal control (126-129 μg/L). (3) The ET in renal cortex homogenate of nephrotic rat of the 4 time points was 364.6, 652.3, 1 526.8, 1 393.6 pg/g, all of that was much more higher than that of normal rat [(235.9-246.1） pg/g,P＜0.05]. (4) The plasma NO in nephrotic rat of the 4 time points was 40, 36, 8 and 11(μmol/L), there was considerable difference through day 8 to day 56 than control (42-46 μmol/L, P＜0.05). (5) The NO in renal cortex homogenate of nephrotic rat was 80, 69, 8, 25 μmol/L that of normal rat was (114-124) μmol/L, there was significant difference between nephrotic rat and control from day 4 through day 56( P＜0.05). (6) The correlation coefficient of plasma ET and NO with separately urinary protein excretion shown statistic significance on only day 8 and day 56, while all of that of ET and NO in renal homogenate closely related with urinary protein from day 4 through to day 56. CONCLUSION： The ET and NO produced locally in renal play more important role in the development of proteinuria.%目的：为明确肾局部内皮素（ET）和一氧化氮（NO）在蛋白尿产生中的作用，作者观察了阿霉素肾病鼠血浆及肾皮质ET、NO含量在蛋白尿发生发展过程中的变化及其与尿蛋白含量的关系。方法：（1）一次性注射法复制大鼠阿霉素肾病综合征模型，并隔日留24h尿测取尿蛋白含量；（2）分别于蛋白尿前期、上升期、高峰期及下降期取血浆及肾皮质匀浆，用放射免疫法检测ET含量，用Griess法检测NO代谢产物NO-2代表NO水平；（3）分别研究了血浆及肾皮质中ET、NO与尿蛋白量两两间的相关性。结果：正常鼠尿蛋白排泌量4-7（mg/d），肾病鼠4个时间点尿蛋白排泌量分别为5、10、241和201mg/d，于蛋白尿上升期始有显著意义的增加，32d为高峰期，56d有所下降。蛋白尿前期、上升期、高峰期和下降期的血浆ET值分别为134、150、538、445ng/L，自上升期始明显高于同期对照组（126-129ng/L）；肾皮质ET分别为364.6、653.3、1526.8、1393.6pg/g肾皮质，自蛋白尿前期始均明显高于对照组（235.9-246.1pg/g，P＜0.05）；4个时点血浆NO-2值分别为40、36、8、11μmol/L，自上升期始明显低于对照组（42-46μmol/L）；肾皮质NO-2值分别为80、69、8、25nmol/g肾皮质，自蛋白尿前期始明显低于对照组（114-124nmol/g，P＜0.05）。上升期血浆ET和下降期血浆NO2-与尿蛋白含量密切相关,而肾皮质ET和NO均自蛋白尿前期始便密切相关于尿蛋白排泌量（P＜0.05）。结论：在蛋白尿发生发展过程中血浆和肾皮质ET、NO均有显著改变，而肾皮质ET、NO含量的改变在蛋白尿的发生发展中起重要作用。
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