Loop diuretic infusion increases thiazide-sensitive NA+/Cl--cotransporter abundance

Role of aldosterone

J. G. Abdallah, R. W. Schrier, C. Edelstein, S. D. Jennings, B. Wyse, David Ellison

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Chronic infusion of loop diuretics into animals induces structural and functional changes in the distal nephron. These changes include increases in the activity of the thiazide-sensitive Na+/Cl--cotransporter (NCC). The NCC was recently demonstrated to be an aldosterone-induced protein. These experiments were designed to test the hypotheses that chronic loop diuretic infusion, with replacement of NaCl losses, increases NCC protein abundance and that this effect results, in part, from stimulation by aldosterone. Sprague-Dawley rats received vehicle (group 1), furosemide (22 mg/100 g body wt per d) (group 2), or furosemide plus spironolactone (22 and 20 mg/100 g body wt per d, respectively) (group 3). Urine output was higher for groups 2 and 3 than for group 1 (151 ± 32, 149 ± 24, and 12 ± 4 ml, respectively; P <0.0001). Immunoblot analysis of NCC protein demonstrated that loop diuretics increased NCC protein abundance by nearly 100% (from 2562 ± 30 to 5248 ± 151 arbitrary units, P <0.01). Spironolactone decreased NCC protein abundance by 66% (to 3532 ± 113 units), compared with the furosemide-treated group (P <0.005). Northern blot analysis of NCC mRNA demonstrated no significant effect of furosemide (NCC/glyceraldehyde-3-phosphate dehydrogenase ratios: group 1, 0.6 ± 0.12; group 2, 0.5 ± 0.05; P > 0.05, NS) These results indicate that increased NCC activity during chronic loop diuretic infusion is associated with increases in NCC protein abundance. A portion of the furosemide effect can be prevented by blockade of mineralocorticoid receptors.

Original languageEnglish (US)
Pages (from-to)1335-1341
Number of pages7
JournalJournal of the American Society of Nephrology
Volume12
Issue number7
StatePublished - 2001

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Member 3 Solute Carrier Family 12
Sodium Potassium Chloride Symporter Inhibitors
Thiazides
Aldosterone
Furosemide
Mineralocorticoid Receptors
Spironolactone
Proteins
Nephrons
Sprague Dawley Rats
Urine

ASJC Scopus subject areas

  • Nephrology

Cite this

Loop diuretic infusion increases thiazide-sensitive NA+/Cl--cotransporter abundance : Role of aldosterone. / Abdallah, J. G.; Schrier, R. W.; Edelstein, C.; Jennings, S. D.; Wyse, B.; Ellison, David.

In: Journal of the American Society of Nephrology, Vol. 12, No. 7, 2001, p. 1335-1341.

Research output: Contribution to journalArticle

Abdallah, J. G. ; Schrier, R. W. ; Edelstein, C. ; Jennings, S. D. ; Wyse, B. ; Ellison, David. / Loop diuretic infusion increases thiazide-sensitive NA+/Cl--cotransporter abundance : Role of aldosterone. In: Journal of the American Society of Nephrology. 2001 ; Vol. 12, No. 7. pp. 1335-1341.
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