Renin-Angiotensin System in the Kidney and Oxidative Stress: Local Renin-Angiotensin-Aldosterone System and NADPH Oxidase-Dependent Oxidative Stress in the Kidney

Abstract

The renin-angiotensin system (RAS) plays an important role in the pathogenesis of renal diseases. All of the RAS components
can be found in the kidney, and intrarenal angiotensin II (AngII) is formed by multiple independent mechanisms. There is also
increasing evidence implicating aldosterone as an important factor besides AngII in the pathogenesis of renal diseases. Therefore,
we should include aldosterone as one of the key components of the renin-angiotensin-aldosterone system (RAAS) when trying
to understand how renal diseases are induced and augmented and, in turn, how they can be suppressed. Although multiple pathways
are involved in the RAAS-dependent renal injury, there is increasing evidence supporting the roles of reactive oxygen species
(ROS), which contribute to renal functional aberrations and pro-inflammatory or pro-fibrotic tissue damages. Animal studies
have shown that AngII- and aldosterone-dependent renal injury is associated with increased ROS production and nicotinamide
adenine dinucleotide phosphate (NADPH) oxidase activity. Furthermore, preclinical and clinical studies have indicated that
the reno-protective effects of RAAS inhibitors are associated with their antioxidative effects. In this chapter, we will briefly
summarize our current understanding of the role of ROS in mediating RAAS-dependent renal injury with special emphasis on the
role of NADPH oxidase.

KeywordsReactive oxygen species-NADPH oxidase-RAAS blockade