P-584: Aminoguanidine does not prevent glomerular hyperfiltration in diabetic rats

• Published in: American journal of hypertension 2001-04, Vol.14 (S1), p.225A-225A
• Main Authors: Cosenzi, Alessandro, Bernobich, Elena, Bonavita, Michela, Bertola, Giuliana, Trevisan, Roberto, Seculin, Paolo, Gris, Furio, Bellini, Giuseppe
• Format: Article
• Language: English
• Subjects: Aminoguanidine; Diabetes; Kidney
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(01)01891-X

Increased urinary excretion of NO metabolites has been demonstrated in the early stages of diabetic nephropathy, suggesting a role for NO in bringing about glomerular hyperfiltration, the main pathogenetic mechanism of this nephropathy. The authors have previously shown increased renal content of iNOS early on in diabetic rats. Therefore the aim of this study was to evaluate whether it was possible to prevent increased glomerular filtration and urinary protein excretion by blocking iNOS in diabetic rats. Forty male WKY rats were divided into two groups: diabetes was induced in 20 animals by streptozotocin i.v. whereas 20 received placebo; 10 diabetic and 10 control rats received aminoguanidine in the drinking water. After 4 weeks the animals were sacrificed. Blood samples and 24-hours urine were collected at the beginning and end of the study. Serum and urinary creatinine were measured and creatinine clearance was calculated; urinary protein excretion was assayed. All data were compared by means of one-way variance analysis and Duncan range. The results show that at the end of study the glomerular filtration rate (Creatinine clearance) was significantly higher (Sig F < 0.02)in diabetic animals than in controls and that this change was not prevented by aminoguadinidine. Urinary protein excretion was also significantly increased in diabetic rats (Sig. F < 0.0001) and aminoguanidine did not prevent this change. Aminoguanidine is a selective inhibitor of iNOS and reduces the production of AGE. However, in our study this substance had no effect on glomerular hyperfiltration and on increased urinary protein excretion. Therefore these results suggest that other isoforms of NOS might be involved in the increased production of NO observed in the early stage of diabetes.