Effects Of L-Arginine And Aminoguanidine On Nitric Oxide, Nitric Oxide Sythase And Urinary Protein Excretion

ObjectiveTo investigate the effects of L-arginine(L-arg) and aminoguanidine(AG) on serum nitric oxide(NO), nitric oxide synthase (NOS) activity and twenty-four hours urinary protein excretion(24hUPE) in early diabetes mellitus (DM) rats,to study the functions of NO in diabetic nephropathy development and the therapeutic effects of L-Arg and AG on diabetic nephropathy.MethodsSixty healthy Wistar rats were involved in the study. The 24 hr urinary protein excretion, serum levels of NO, total nitric oxide synthase (tNOS) activity, inducible nitric oxide (iNOS) synthase activity and constructive nitric oxide synthase (cNOS) activity were detected to the rats. Streptozotocin (60mg.kg") was administrated in the rats. The Streptozotocin diabetic rats were randomly divided into diabetes control group, L-arginine group and Aminoguanidine group. At the end of 8 weeks after STZ administration, the above five indexes of the rats were detected and statistical analysis was carried out. SPSS 10.0 was used in the process of medical software processingprocess.The results were shown in terms of x ± S results.T-tests were made amongthe different models of DM at the end of 8th week. The analyses of variance were made and then the Student-Newman-Keuls (SNK) method was used in the comparisons (P<0.05). The relativity of NO and the twenty-four-hour urinary proteinexcretion was made according to linear correlational analyses.Results1. compared with normal rats, 24hUPE, iNOS and NO of the rats in DM control group increased significantly (P<0.01, P<0.05), In the rats of AG group, 24hUPE increased while both tNOS, iNOS and cNOS decreased (P<0.01, P<0.05).2. Compared with the diabetes control group , both 24hUPE and NO increased (P<0.05) in L-Arg group at the end of 8 weeks. There was no obvious differences in tNOS, iNOS and cNOS levels in L-arginine group, and the five indexes were significantly decreased in AG group (P<0.05). Compared with L-Arg group, the five indexes were obviously decreased in AG group (P<0.05).ConclusionIn the STZ-induced DM rats, NO plays an important role in the pathogenic mechanism of diabetic nephropathy. In the progress of DM, the early administration of L-arginine can increase the level of NO and the twenty-four-hour urinary protein excretion, may cause more renal damages.Therefore the early administration of aminoguanidine can effectively reduce the twenty-four-hour urinary protein excretion and renal injury by decreasing the NOS activity, NO level and other more important mechanisms.