Oxidative stress and hypertension

Abstract 

Mammalian cells are capable of generating metabolites of oxygen, referred to as reactive oxygen species (ROS) via the action of several enzymes. In vascular cells, ROS are predominantly produced by the NADPH oxidases, uncoupled nitric oxide synthase, xanthine oxidase and by mitochondrial sources. In hypertension, ROS production by these sources is increased, and this not only contributes to hypertension, but also causes vascular disease and dysfunction. ROS production in other organs, particularly the kidney and the centers within the brain, likely participate in blood pressure regulation. Despite the wealth of data supporting a role of ROS in hypertension and other cardiovascular diseases, treatment with commonly employed antioxidants have failed, and in some cases have proven harmful, prompting a reconsideration of the concept of oxidative stress. Within the cell, ROS are produced locally and have important signaling roles, such that scavenging of these species by exogenous antioxidants is difficult and could produce untoward effects. In this article, we consider these tissues and discuss potential new approaches to treatment of “oxidative stress”.

Keywords: NADPH oxidase, tetrahydrobiopterin, nitric oxide, superoxide, Nox enzymes, multidrug resistance protein 1