Renal oxidative stress in medullary thick ascending limbs produced by elevated NaCl and glucose. Hypertension 2004 Feb;43(2):341-6
Date
01/14/2004Pubmed ID
14718354DOI
10.1161/01.HYP.0000113295.31481.36Scopus ID
2-s2.0-0842268296 (requires institutional sign-in at Scopus site) 70 CitationsAbstract
The effects of NaCl, glucose, and thyroid hormone on the production of superoxide (O2*-) within the renal medulla of Sprague-Dawley rats were examined. Responses of intracellular superoxide [O2*-]i in isolated medullary thick ascending limbs (mTALs) were studied using real-time fluorescent microscopy with measurement of the dehydroethidium (DHE) to ethidium (Eth) conversion ratio (Eth/DHE ratio unit). The results demonstrated that elevations of extracellular NaCl (from 152 to 252 mmol/L), D-glucose (from 5 to 25 mmol/L), and triiodo-thyronine (T3; 10 micromol/L) significantly increased [O2*-]i levels. Preincubation with superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (1 mmol/L) significantly inhibited these responses. Stimulation with equamolar amounts of choline chloride or L-glucose failed to increase [O2*]i, indicating that these O2*- responses were not determined by changes in osmolality. The responses to NaCl, D-glucose, and T3 were abolished by pretreatment with the Na+/K+-ATPase pump inhibitor ouabain (4 mmol/L) and with Na+/H+ -exchanger inhibitor dimethylamiloride (100 micromol/L). We conclude that elevations of extracellular NaCl, D-glucose, or T3 levels can activate both the Na+/K+-ATPase pump and Na+/H+ exchanger in mTAL, which, in turn, is associated with increased intracellular concentrations of superoxide.
Author List
Mori T, Cowley AW JrAuthor
Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCulture Techniques
Glucose
Kidney Medulla
Loop of Henle
Male
Oxidative Stress
Rats
Rats, Sprague-Dawley
Sodium Chloride
Sodium-Hydrogen Exchangers
Sodium-Potassium-Exchanging ATPase
Superoxides
Triiodothyronine