Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

Allen W. Cowley, Michiaki Abe, Takefumi Mori, Paul M O'Connor, Yusuke Ohsaki, Nadezhda N. Zheleznova

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)F179-F197
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number3
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Reactive Oxygen Species
Sodium
Hypertension
Extremities
Kidney
Superoxides
Hydrogen Peroxide
Nitric Oxide
Salts
Inbred Dahl Rats
Water
NADPH Oxidase
Rectum
Oxidation-Reduction
Mitochondria
Homeostasis
Ischemia
Adenosine Triphosphate
Blood Pressure
Membranes

Keywords

  • Dahl SS rats
  • Hydrogen peroxide (HO)
  • Kidney
  • MTAL
  • Medullary blood flow
  • NAD(P)H oxidase
  • Nitric oxide (NO)
  • Superoxide (O·)

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. / Cowley, Allen W.; Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M; Ohsaki, Yusuke; Zheleznova, Nadezhda N.

In: American Journal of Physiology - Renal Physiology, Vol. 308, No. 3, 01.01.2015, p. F179-F197.

Research output: Contribution to journalArticle

Cowley, Allen W. ; Abe, Michiaki ; Mori, Takefumi ; O'Connor, Paul M ; Ohsaki, Yusuke ; Zheleznova, Nadezhda N. / Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. In: American Journal of Physiology - Renal Physiology. 2015 ; Vol. 308, No. 3. pp. F179-F197.
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