Reactive oxygen species in hypertension

Hypertension is a leading risk factor for stroke, heart disease and chronic kidney disease. Multiple interacting factors and organ systems increase blood pressure and cause target-organ damage. Among the many molecular elements involved in the development of hypertension are reactive oxygen species (ROS), which influence cellular processes in systems that contribute to blood pressure elevation (such as the cardiovascular, renal, immune and central nervous systems, or the renin–angiotensin–aldosterone system). Dysregulated ROS production (oxidative stress) is a hallmark of hypertension in humans and experimental models. Of the many ROS-generating enzymes, NADPH oxidases are the most important in the development of hypertension. At the cellular level, ROS influence signalling pathways that define cell fate and function. Oxidative stress promotes aberrant redox signalling and cell injury, causing endothelial dysfunction, vascular damage, cardiovascular remodelling, inflammation and renal injury, which are all important in both the causes and consequences of hypertension. ROS scavengers reduce blood pressure in almost all experimental models of hypertension; however, clinical trials of antioxidants have yielded mixed results. In this Review, we highlight the latest advances in the understanding of the role and the clinical implications of ROS in hypertension. We focus on cellular sources of ROS, molecular mechanisms of oxidative stress and alterations in redox signalling in organ systems, and their contributions to hypertension. In this Review, Touyz and colleagues discuss the role of reactive oxygen species in the pathophysiology of hypertension, focusing on the mechanisms of reactive oxygen species generation and oxidative stress in hypertension, as well as the alterations in redox signalling. They also discuss potential therapeutic strategies for targeting oxidative stress in hypertension. Key points Hypertension is a multisystem, polygenic and complex condition and is a leading cause of morbidity and premature death globally. The aetiology of hypertension is unknown in 90–95% of patients. At the molecular level, hypertension is associated with increased bioavailability of reactive oxygen species (ROS), leading to oxidative stress. A major cause of oxidative stress in hypertension is increased generation of ROS owing primarily to activation of the ROS-producing enzymes NADPH oxidases (NOX), which comprise seven members, with NOX1, NOX2, NOX4 and NOX5 having