Role of angiotensin II on protein expression of renal nitric oxide synthase in unilateral ureteral obstructive rat

Abstract

Background: In the kidney, angiotensin II (ANG II) and nitric oxide (NO) can stimulate each other. Unilateral ureteral obstruction (UUO) activates both substances, where ANG II is stimulated first and NO is augmented later. Objective: Investigate the role of ANG II on renal nitric oxide synthase (NOS) protein expression in UUO. Methods: Male Wistar rats were divided into sham and UUO. The UUO rats were treated separately with water, angiotensin converting enzyme inhibitor (ACEI), or angiotensin receptor type 1 blocker (ARB) for one day before UUO and continuously for one or seven days after the operation. The endothelial NOS (eNOS) and inducible NOS (iNOS) protein expressions were examined in histology. Results: By immunohistochemistry, renal eNOS protein expression in the sham group showed staining in glomerulus and tubular epithelial cells in the cortex and medulla. UUO for one or seven days increased eNOS protein expression. ACEI or ARB reduced the heightened expression caused by UUO in 1-day group. However, in 7-day group, the elevated expression was maintained in the cortex, but was further increased in the medulla after ACEI or ARB administration. Both 1-day and 7-day UUO, with or without angiotensin blockade agents, caused no change in iNOS protein expression. One-day UUO resulted in mild tubular dilatation and cell infiltration. ACEI or ARB could attenuate structural alterations. The 7-day UUO rats demonstrated progressively morphological changes. ACEI was more effective than ARB in reducing tissue destruction. Conclusion: In UUO, 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 nephropathy induced by UUO.