All Oxidase Roads Lead to Angiotensin, Too

Abstract

Free radicals and other oxygen- or nitrogen-derived reactive species formed during cellular metabolism and respiration, like superoxide (O2·−), hydrogen peroxide (H2O2), and nitric oxide (NO), are important second messengers and fundamental mediators in biological processes, redox signaling, and cellular growth. However, over the past 2 decades it has become clear that reactive oxygen species (ROS) in particular are also important participants in a number of pathological processes, including cardiovascular and kidney diseases. In fact, increased production of ROS has been proposed as a common pathomechanism by which cardiovascular risk factors affect the vessel wall to induce and amplify vessel and organ injury. See page 943 Several possible enzymatic sources of ROS have been identified in blood vessels and other tissues, such as nicotineamide adenine dinucleotide (phosphate) oxidase (NAD(P)H oxidase), xanthine oxidase (XO), and uncoupled nitric oxide synthase. NAD(P)H oxidase has long been considered one of the most important sources of ROS in the vessel wall. One of its most potent stimulants is angiotensin II. In turn, NAD(P)H oxidase mediates several downstream effects of angiotensin II like inflammation, endothelial dysfunction, collagen deposition, and vascular hypertrophy. Nevertheless, an important role in the pathogenesis of cardiovascular disease has also been ascribed to XO. This …