Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb

Michiaki Abe, Paul O'Connor, Mary Kaldunski, Mingyu Liang, Richard J. Roman, Allen W. Cowley

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl-. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.

Original languageEnglish (US)
Pages (from-to)F350-F357
JournalAmerican Journal of Physiology - Renal Physiology
Volume291
Issue number2
DOIs
StatePublished - Aug 4 2006

Fingerprint

Superoxides
Nitric Oxide
Extremities
Sodium
Hypertension
Kidney
Active Biological Transport
Ouabain
Choline
Osmolar Concentration
Biological Availability
Oxidative Stress
Necrosis
Coloring Agents
Perfusion
Pressure
Wounds and Injuries

Keywords

  • Hypertension
  • Renal perfusion pressure

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. / Abe, Michiaki; O'Connor, Paul; Kaldunski, Mary; Liang, Mingyu; Roman, Richard J.; Cowley, Allen W.

In: American Journal of Physiology - Renal Physiology, Vol. 291, No. 2, 04.08.2006, p. F350-F357.

Research output: Contribution to journalArticle

Abe, Michiaki ; O'Connor, Paul ; Kaldunski, Mary ; Liang, Mingyu ; Roman, Richard J. ; Cowley, Allen W. / Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. In: American Journal of Physiology - Renal Physiology. 2006 ; Vol. 291, No. 2. pp. F350-F357.
@article{974aded85c534315a71b10dd1640e999,
title = "Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb",
abstract = "Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl-. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.",
keywords = "Hypertension, Renal perfusion pressure",
author = "Michiaki Abe and Paul O'Connor and Mary Kaldunski and Mingyu Liang and Roman, {Richard J.} and Cowley, {Allen W.}",
year = "2006",
month = "8",
day = "4",
doi = "10.1152/ajprenal.00407.2005",
language = "English (US)",
volume = "291",
pages = "F350--F357",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2",

}

TY - JOUR

T1 - Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb

AU - Abe, Michiaki

AU - O'Connor, Paul

AU - Kaldunski, Mary

AU - Liang, Mingyu

AU - Roman, Richard J.

AU - Cowley, Allen W.

PY - 2006/8/4

Y1 - 2006/8/4

N2 - Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl-. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.

AB - Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl-. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.

KW - Hypertension

KW - Renal perfusion pressure

UR - http://www.scopus.com/inward/record.url?scp=33746583565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746583565&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00407.2005

DO - 10.1152/ajprenal.00407.2005

M3 - Article

C2 - 16597609

AN - SCOPUS:33746583565

VL - 291

SP - F350-F357

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 2

ER -