Abstract
Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization, and cellular signaling. Increased ROS production (termed "oxidative stress") has been implicated in various pathologies, including hypertension, atherosclerosis, diabetes, and chronic kidney disease. A major source for vascular and renal ROS is a family of nonphagocytic NAD(P)H oxidases, including the prototypic Nox2 homolog-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. NAD(P)H oxidase-derived ROS plays a physiological role in the regulation of endothelial function and vascular tone and a pathophysiological role in endothelial dysfunction, inflammation, hypertrophy, apoptosis, migration, fibrosis, angiogenesis, and rarefaction, important processes underlying cardiovascular and renal remodeling in hypertension and diabetes. These findings have evoked considerable interest because of the possibilities that therapies 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 renal dysfunction and thereby prevent or regress target organ damage associated with hypertension and diabetes. Here we highlight current developments in the field of reactive oxygen species and cardiovascular disease, focusing specifically on the recently identified novel Nox family of NAD(P)H oxidases in hypertension. We also discuss the potential role of targeting ROS as a therapeutic possibility in the management of hypertension and cardiovascular disease.
Highlights
Reactive oxygen species (ROS) play an important role in the development of cardiovascular disease, including hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke
1⁄7O2Ϫ is shortlived owing to its rapid reduction to H2O2 by superoxide dismutase (SOD) (9)
2vtwa1⁄7Osece2unϪlacϩretlil2ssHs.uTϩehi3es tmhHea2idnOis2smoϩuurtOcaet2i.ooTnf hHoif2s1⁄7OOre22aϪicn-: tion can be spontaneous or it can be catalyzed by SOD, of which there are three mammalian isoforms: copper/zinc SOD
Summary
Reactive oxygen species (ROS) influence many physiological processes including host defense, hormone biosynthesis, fertilization, and cellular signaling. Agents that reduce oxidant formation should be more efficacious than nonspecific inefficient antioxidant scavengers in ameliorating oxidative stress This is based on experimental evidence where it has been clearly demonstrated that inhibition of NAD(P)H oxidase–mediated 1⁄7O2Ϫ generation, using pharmacological and gene-targeted strategies, leads to regression of vascular remodeling, improved endothelial function, and lowering of blood pressure (44,74,81). Antioxidant supplementation is not recommended for the prevention or treatment of hypertension This advice, which is consistent with the guidelines of the American Heart Association (146) and the Canadian Hypertension Society (147), considers the role of the total diet in influencing disease risk and is supported by findings from the Dietary Approaches to Stop Hypertension (DASH) study (142) and a recent trial from the U.K. that demonstrated that subjects consuming high fruit and vegetable diets had significantly reduced blood pressure (141).
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