Reactive oxygen species and vascular biology: implications in human hypertension

Increased vascular production of reactive oxygen species (ROS; termed oxidative stress) has been implicated in various chronic diseases, including hypertension. Oxidative stress is both a cause and a consequence of hypertension. Although oxidative injury may not be the sole etiology, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, vessels and possibly the immune system. Compelling experimental and clinical evidence indicates the importance of the vasculature in the pathophysiology of hypertension and as such much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular, renal and neural ROS is a family of non-phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox), including the prototypic Nox2 homolog-based NADPH oxidase, as well as other Noxes, such as Nox1 and Nox4. Nox-derived ROS is important in regulating endothelial function and vascular tone. Oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis and rarefaction, important processes involved in vascular remodeling in hypertension. Despite a plethora of data implicating oxidative stress as a causative factor in experimental hypertension, findings in human hypertension are less conclusive. This review highlights the importance of ROS in vascular biology and focuses on the potential role of oxidative stress in human hypertension

Reactive oxygen species, vascular disease, and hypertension

Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization, and cellular signaling. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in chronic diseases including atherosclerosis and hypertension. Although oxidative injury may not be the sole etiology of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin system, and sympathetic hyperactivity. Oxidative stress is a multisystem phenomenon in hypertension and involves the heart, kidneys, nervous system, and vessels. A major source for cardiovascular, renal, and neural ROS is a family of non-phagocytic NADPH oxidases, including the prototypic Nox2 homologue-based NADPH oxidase, as well as other NADPH oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase (NOS). Cross talk between Noxes and mitochondrial oxidases is increasingly implicated in cellular ROS production. Convincing findings from experimental and animal studies support a causative role for oxidative stress in the pathogenesis of hypertension. However, there is still no solid evidence that oxidative stress is fundamentally involved in the pathogenesis of human hypertension. Reasons for this are complex and relate to heterogeneity of populations studied, inappropriate or insensitive methodologies to evaluate oxidative state clinically, and suboptimal antioxidant therapies used. Nevertheless, what is becoming increasingly evident is that oxidative stress is important in the molecular mechanisms associated with cardiovascular and renal injury in hypertension and that hypertension itself can contribute to oxidative stress. This chapter provides a comprehensive review of the role of ROS in the (patho)physiology of vascular injury and discusses the importance of Noxes in vascular oxidative stress. Implications in experimental and human hypertension are highlighted