Role of angiotensin system on renal nitric oxide synthase and nitric oxide production in unilateral ureteral obstructive rat

Abstract

This study was conducted to investigate the role of angiotensin on renal nitric oxide synthase (NOS) protein expression and nitric oxide (NO) production in unilateral ureteral obstruction (UUO). Male Wistar rats were divided into two main groups: sham operation and UUO. In UUO groups, the animals were further divided into 3 subgroups (n = 8 in each group) treated with: 1) water 2) water + angiotensin converting enzyme inhibitor (ACEI; Enalapril® ; 200 mg/L) (UUO+ACEI) and 3) water + angiotensin II receptor type 1 antagonist (ARA; Losartan® 500 mg/L) (UUO+ARA). The treatment was performed one day before the operation (Sham or UUO) and continuously for 1 day or 7 days after the operation. On each experimental due date, 24-hr urine and blood samples were collected. The serum was stored at -80℃ until use for measurement of NO production (nitrite), electrolytes, blood urea nitrogen (BUN), creatinine (Cr), and Cr clearance (C[subscript cr]). The kidneys were removed and fixed for endothelial NOS (eNOS) protein expression and histological study. By immunohistochemistry, the expression of renal eNOS protein showed the staining in glomerulus as well as in renal tubular epithelial cells in both cortex and medulla. UUO for 1 or 7 days caused an increase in eNOS protein expression. Treatment with either ACEI or ARA slightly reduced the expression caused by UUO in 1-day group. However, in 7- day animals, the expression was maintained in cortex and was further increased in medulla after ACEI or ARA administration. One day and seven days after UUO, serum nitrite concentration was significantly increased (p<0.05). The treatment with ACEI and ARA could normalize the heightened nitrite level induced by UUO to be that of the sham animals. The 1-day UUO kidney showed a mild tubular dilatation and some cell infiltration. Both ACEI and ARA could attenuate structural alterations. The 7-day UUO rats demonstrated progressively morphological changes. The ACEI had more effectiveness in reduction of tissue destruction than those of ARA. The values of electrolyte, Cr, BUN of C[subscript cr] in all experimental groups were in normal range. The present data are the evidence of UUO model in that angiotensin blockade could attenuate renal eNOS protein expression in 1-day UUO group but not in 7-day UUO animals. The inhibition of angiotensin system ameliorates increased NO production and nephropathy induced by UUO.