The development of oxidant stress in renal interstitial fibrosis: Role of angiotensin II

The development of interstitial fibrosis is an important determinant of renal impairment. The present study evaluates the importance of angiotensin 11 (All) in mediation of reactive oxygen/nitrogen species-induced cell injury and antioxidant enzyme dysfunction leading to the development of interstitial fibrosis. Male Sprague-Dawley rats underwent unilateral ureteral obstruction (UUO) with/without administration of candesartan, an All receptor (AT(1)) inhibitor. Northern blot analysis and antioxidant protein activity demonstrated a restored pattern of Cu-Zn superoxide dismutase (Cu-ZnSOD) and catalase mRNA expression, when UUO rats were administered candesartan. Western blot analysis revealed that candesartan pretreatment of UUO rats significantly decreased nitrotyrosine protein levels, a marker of peroxynitrite production and inducible nitric oxide synthase (iNOS) protein expression, compared to the obstructed kidneys. These studies demonstrate a protective effect of AT, receptor inhibition in UUO rats following a restoration of renal cortical antioxidant status, decreased iNOS and peroxynitrite protein expression, important mediators of extracellular matrix (ECM) accumulation leading to the development of interstitial fibrosis.