Oxidative Stress in Hypertension: Role of the Kidney

Abstract

Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H 2 O 2 ) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the reninangiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O 2 -rather than H 2 O 2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renaldamaging effects of hypertension. Antioxid. Redox Signal. 20, 74-101.

Role of Nox4 and p67phox subunit of Nox2 in ROS production in response to increased tubular flow in the mTAL of Dahl salt-sensitive rats

“…We have found that elevated ROS production within the renal outer medulla of SS rats can be largely attributed to the multicomponent NADPH oxidases (Nox) (45) that catalyze the reduction of molecular oxygen to superoxide (O 2 ·Ϫ ) and H 2 O 2 . Among the seven different members of the Nox family of enzymes, Nox2 (also named gp91phox) and Nox4 are expressed in the kidneys of rats (3,5,18,21,22,30). Our data and findings of others indicate that Nox1 is expressed at very low levels in the medullary thick ascending limb of Henle (mTAL), and Nox5 has not been found in rodents (15,21,30).…”

Oxidant Mechanisms in Renal Injury and Disease

“…For instance, dysregulation of antioxidants, particularly catalase and peroxidases, results in the accumulation of hydrogen peroxide, which can react with transition metals to subsequently form highly reactive and damaging species with reactivities, such as the hydroxyl radical. Furthermore, studies indicate the overproduction of superoxide, primarily by NADPH oxidase and mitochondria, and reduced superoxide metabolism by SOD and other antioxidants, can initiate or potentiate the development of hypertension (8). For example, it has been shown that during the onset of hypertension, patients have 7% lower antioxidant capacity, including decreased erythrocyte catalase content and enhanced oxidation of low-density lipoproteins (LDLs) (45, 266).…”

“…As NADPH oxidase transfers electrons from NADPH, they react with oxygen to form superoxide, which is usually rapidly converted to hydrogen peroxide. All of the components necessary for NADPH oxidase to function are present in the kidney, including the presence of four different isoforms of this oxidase-NOX1, NOX2, NOX4, and NOX5 (8,33,112). The expression of these different NADPH oxidase isoform components has been observed throughout the cortex and medulla of the mammalian (including human) kidney, including in the mesangium (97,136,184,190), proximal convoluted tubules, distal convoluted tubules, collecting duct, macula densa (17,77,139,217,281,309,322), endothelium, and VSMCs (8).…”

Oxidation During Digestion of Meat: Interactions with the Diet andHelicobacter pyloriGastritis, and Implications on Human Health

“…These observations may help explain why there is an epidemiological association between high consumption of processed meat, which is typically high in fat, but not high red meat consumption, with coronary heart disease risk (Micha and others 2010) and hypertension (Lajous and others 2014). After all, renal oxidative stress has been suggested to contribute to hypertension by inducing renal vasoconstriction and renin release, among other mechanisms (Araujo and Wilcox 2014), and cardiac oxidative stress may lead to cardiac hypertrophy (Maulik and Kumar 2012). However, another study showed that L-carnitine, a compound abundantly present in beef, protected the heart and liver against oxidation in an atherosclerotic rat model (Dayanandan and others 2001).…”