Reactive Oxygen Species, Oxidative Stress, and Hypertension

Abstract

Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization and cellular signaling. Increased ROS production has been implicated in various chronic diseases, including hypertension, atherosclerosis, diabetes and kidney disease. Oxidative stress may be 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 prohypertensive 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. Compelling evidence indicates the importance of the vasculature in the pathophysiology of hypertension, and therefore much emphasis has been placed on the (patho)biology of ROS in the vascular system. A major source for cardiovascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homologue-based NAD(P)H oxidase, as well as other NAD(P)H oxidases, such as Nox1 and Nox4. Other possible sources include mitochondrial electron transport enzymes, xanthine oxidase, cyclooxygenase, lipoxygenase, and uncoupled nitric oxide synthase (NOS). NAD(P)H oxidase-derived ROS is important in regulating endothelial function and vascular tone, and oxidative stress is implicated in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes involved in vascular remodeling in hypertension. These findings have evoked considerable interest because of the possibilities that therapies targeted against nonphagocytic NAD(P)H oxidase to decrease ROS generation and/or strategies to increase nitric oxide (NO) availability and antioxidants may be useful in minimizing vascular injury and thereby prevent or regress target organ damage associated with hypertension.