Role of Renin-Angiotensin System and Nuclear Factor-κB in the Obstructed Kidney of Rats With Unilateral Ureteral Obstruction

Abstract

The present study was conducted to elucidate the role of oxidative stress and nuclear factor-κB (NF-κB) in the beneficial effects of angiotensin receptor blockade on obstructive nephropathy. Unilateral ureteral occlusion in rats elicited tubulo-interstitial fibrosis with concomitant macrophage infiltration and increased expression of monocyte chemoattractant protein-1. These changes were accompanied by an induction of renal cortical lipid peroxidation and activation of NF-κB. Both an AT₁ antagonist, candesartan, and a NF-κB inhibitor, pyrrolidine dithiocarbamate, markedly attenuated these changes and to a similar extent. These results suggest that the beneficial effects of angiotensin blockade are mediated by the inhibition of oxidative stress and subsequent NF-κB activation in obstructive nephropathy.