One Step Beyond

Abstract

Much evidence supports the role of increased levels of reactive oxygen species (ROS) in the pathogenesis of cardiovascular diseases, including hypertension. The increased activity and expression of the reduced nicotinamide-adenine dinucleotide phosphate oxidase observed in hypertensive populations have implicated the superoxide anion as one of the main species responsible. This view has been supported by studies demonstrating vascular-protective effects of the superoxide dismutase family, enzymes that remove superoxide anion thereby protecting the bioavailability of NO.1 Despite this, it has proven particularly difficult to identify those genetic and environmental factors, relating to ROS metabolism, that contribute to the development of vascular dysfunction. The article by Chrissobolis et al2 in this issue of Hypertension serves to remind us that we need to look one step beyond those mechanisms directly involving superoxide anion and superoxide dismutase. Indeed, hydrogen peroxide (H2O2), the end product of the superoxide dismutases, has been shown to have vascular reactive properties and can impair NO-mediated signaling in blood vessels by a variety of mechanisms. Looking beyond superoxide dismutase will undoubtedly help us to more comprehensively understand the roles of ROS in vascular function and disease.3 Perhaps this will assist in the identification of those elusive genes suspected, but so far undefined, in the pathogenesis of high blood pressure. Chrissobolis et al2 explored the effects of modulating the activity of glutathione peroxidase-1 (GPX1), an enzyme that catalyzes the …