Faculty Collaboration Database

Enhanced amiloride-sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2008 Sep;295(3):F726-33

Date

06/27/2008

Pubmed ID

18579705

Pubmed Central ID

PMC2536875

DOI

10.1152/ajprenal.00137.2008

Scopus ID

2-s2.0-54449098442 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

The aims of the present study were to determine whether superoxide (O(2)(-)) production is enhanced in medullary thick ascending limb (mTAL) of Dahl salt-sensitive (SS) rats compared with a salt-resistant consomic control strain (SS.13(BN)) and to elucidate the cellular pathways responsible for augmented O(2)(-) production. Studies were carried out in 7- to 10-wk-old male SS and SS.13(BN) rats fed either a 0.4% NaCl diet or a 4.0% NaCl diet for 3 days before tissue harvest. Tissue strips containing mTAL were isolated from the left kidney, loaded with the O(2)(-)-sensitive fluorescent dye dihydroethidium, superfused with modified Hanks' solution, and imaged at x60 magnification on a heated microscope stage. O(2)(-) production was stimulated in mTAL by incrementing superfusate NaCl concentration from 154 to 254 to 500 mM. O(2)(-) production was enhanced in mTAL of SS rats compared with SS.13(BN) rats in response to incrementing bath NaCl. Addition of N-methyl-amiloride (100 muM) or inhibition of NAD(P)H oxidase reduced O(2)(-) production in SS mTAL to levels observed in SS.13(BN) rats. Both amiloride- and ouabain-sensitive pathways of O(2)(-) production were elevated following 3 days of high (4.0%) NaCl feeding in mTAL of SS and SS.13(BN) rats. We conclude that mTAL from SS rats exhibit enhanced amiloride-sensitive O(2)(-) production. The amiloride-sensitive O(2)(-) response in mTAL is independent of active Na(+) transport and appears to be mediated by NAD(P)H oxidase. Amiloride-sensitive O(2)(-) production is likely to contribute to augmented outer medullary O(2)(-) production observed in SS rats during both normal and high NaCl diets.

Author List

O'Connor PM, Lu L, Schreck C, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amiloride
Animals
Cell Size
Disease Models, Animal
Epithelial Cells
Extracellular Fluid
Hypertension
In Vitro Techniques
Kidney Medulla
Male
NADPH Oxidases
Osmolar Concentration
Oxidative Stress
Rats
Rats, Inbred Dahl
Sodium
Sodium Channel Blockers
Sodium Chloride
Sodium, Dietary
Superoxides
Urothelium