title: Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension.
abstract: The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na(+) reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin cowley@mcw.edu.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Connor
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohsaki
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Nadezhda N
authors.initials: NN
authors.lastname: Zheleznova
mesh_terms: D000818:Animals; D006801:Humans; D007022:Hypotension / Q000378:metabolism*; D007679:Kidney Medulla / Q000098:blood supply*; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D012964:Sodium; D019255:NADPH Oxidases
keywords: Dahl SS rats; NAD(P)H oxidase; hydrogen peroxide (H2O2); kidney; mTAL; medullary blood flow; nitric oxide (NO); superoxide (O2·−)