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, D. H. Ellison

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


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
Issue number7
StatePublished - 2001

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'Loop diuretic infusion increases thiazide-sensitive NA+/Cl--cotransporter abundance: Role of aldosterone'. Together they form a unique fingerprint.

Cite this