Role of Oxidative Stress in Hypertension

Abstract

Oxidative stress refers to an increase in steady-state levels of reactive oxygen spe- cies (ROS), including superoxide (the precursor for multiple ROS), and can be due to increased production of superoxide and reactive nitrogen species [RNS], and/or decreased expression or activity of antioxidant enzymes such as superoxide dis- mutases (SOD’s) and glutathione peroxidises (GPx’s) that regulate subcellular ROS levels [1, 2]. ROS can have direct effects; however, since superoxide reacts extremely efficiently with nitric oxide (NO) to form the RNS peroxynitrite, ROS can reduce NO bioavailability and adversely affect NO signalling, causing endothelial dysfunc- tion. As such, oxidative stress is involved in the pathogenesis of hypertension [3]. Hypertension is a complex condition and a major risk factor for cardiovascular events [4]. Although many of the cases of hypertension have an unknown cause (defined as essential hypertension) [5], there is much experimental evidence sup- porting a role for increased ROS in the pathogenesis of hypertension [6]. The purpose of this chapter is to examine the relationship between oxidative stress and hypertension in experimental models, including the involvement of oxidative stress and novel downstream signalling mechanisms. Vascular NADPH oxidases (Nox) are by far the most researched source of ROS in hypertension, and are thought to be a predominant underlying cause of oxidative stress in numerous chronic cardiovascular diseases [7], and hence will be a major focus of our discus- sion. Antioxidant defence mechanisms (i.e. SOD’s, GPx) may limit vascular oxida- tive stress and protect against hypertension and they will be discussed also. Innate immune cells produce ROS to destroy invading pathogens; however, sustained inflammation can lead to oxidative stress. In addition to being a major source of ROS in the vasculature, NADPH oxidases are also a source of ROS in immune cells [7], thus the recent concept linking the immune system, oxidative stress, and hyper- tension will be examined, and finally we will briefly address clinical data providing an association between oxidative stress and hypertension, in particular the link between genetic abnormalities and oxidative stress in hypertension.