Study of chronic effect of Losartan in inhibition of kidney glomerular number and glomerular volume changes in uninephrectomized diabetic rats(Stereological study).

Abstract

Background: Diabetic nephropathy is one of the cause of the end stage of renal disease (ESRD). Hyperglicemia activate intrarenal Renin-Angiotensin system and highly AngiotensinII is produced locally in glomeruli. In this research AT1(Angiotensin type 1) receptors blocked by Losartan and effects of this drug in inhibition of renal structural lesions were assessed quantitatively. Materials & methods: 24 male rats (2 month ages) were uninephrectomised from left flank and then randomly divided in 3 groups (8 per group), then Diabetes were induced in second and third groups by injection of alloxan tetrahydrate (120 mg/kg) subcutaneously. Five days after diabetes induction third group received losartan (5 mg/kg/day) orally for 8 weeks. After 8 weeks kidneys from all groups were sampled, fixed and each kidney sliced in 1 mm thickness (systematic random sampling) for stereological study. After tissue processing section pairs were made with 5 micron thickness from each slice and stained by PAS method. Kidney volume, glomerular volume and glomerular number estimated by cavalieri and physical disector methods. Results: Significancy test between means variables in groups were analyzed with Mann Withney statistical test in P<0.05 by SPSS12 software. For three variables (kidney volume,glomerular volume and glomerular number) losartan treated group showed significant difference to in comparison nontreated diabetic group. Conclusion: Chronic low dose usage of losartan in uninephrectomized diabetic rats can prevent kidney volume increasing (84%), inhibit increase glomerular volume (67%) and prevent glomerular number decreasing (68%) significantly. Combined drug therapy is recommended for better results.