Aldosterone inhibits HCO3- absorption via a nongenomic pathway in medullary thick ascending limb

David W. Good, Thampi George, Bruns A. Watts

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38 Scopus citations


Rapid actions of aldosterone that are independent of transcription and translation have been described in a variety of cells; however, whether nongenomic pathways mediate aldosterone-induced regulation of renal tubule transport has not been determined. We report here that aldosterone induces rapid (<3.5 min) inhibition of HCO3- absorption in the medullary thick ascending limb (MTAL) of the rat. This inhibition is observed over the physiological range of hormone concentrations (IC50 ≃ 0.6 nM) and is not affected by pretreatment with actinomycin D (12.5 μg/ml), cycloheximide (40 μg/ml), or spironolactone (10 μM). The glucocorticoids dexamethasone, cortisol, and corticosterone (1 or 500 nM) did not affect HCO3- absorption in the absence or presence of carbenoxolone. Thus the specificity of rapid aldosterone action is not dependent on 11β-hydroxysteroid dehydrogenase activity. The inhibition by aldosterone is additive to inhibition by angiotensin II and vasopressin, indicating that these factors regulate MTAL transport through distinct pathways. These results demonstrate that aldosterone inhibits HCO3- absorption in the MTAL via a pathway that is rapid, highly selective, independent of transcription and protein synthesis, and not mediated through the classic mineralocorticoid receptor. The results establish a role for nongenomic pathways in mediating aldosterone-induced regulation of transepithelial transport in the mammalian kidney. The novel action of aldosterone to inhibit luminal acidification in the MTAL may play a role in enabling the kidney to regulate acid-base balance independently of Na+ balance and extracellular fluid volume.

Original languageEnglish (US)
Pages (from-to)F699-F706
JournalAmerican Journal of Physiology - Renal Physiology
Issue number4 52-4
StatePublished - Oct 2002


  • 11β-hydroxysteroid dehydrogenase
  • Acid-base balance
  • Glucocorticoids
  • Kidney
  • Mineralocorticoid receptor

ASJC Scopus subject areas

  • Physiology
  • Urology


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