ANP-stimulated Na+ secretion in the collecting duct prevents Na+ retention in the renal adaptation to acid load

Am J Physiol Renal Physiol. 2019 Aug 1;317(2):F435-F443. doi: 10.1152/ajprenal.00059.2019. Epub 2019 Jun 12.

Abstract

We have recently reported that type A intercalated cells of the collecting duct secrete Na+ by a mechanism coupling the basolateral type 1 Na+-K+-2Cl- cotransporter with apical type 2 H+-K+-ATPase (HKA2) functioning under its Na+/K+ exchange mode. The first aim of the present study was to evaluate whether this secretory pathway is a target of atrial natriuretic peptide (ANP). Despite hyperaldosteronemia, metabolic acidosis is not associated with Na+ retention. The second aim of the present study was to evaluate whether ANP-induced stimulation of Na+ secretion by type A intercalated cells might account for mineralocorticoid escape during metabolic acidosis. In Xenopus oocytes expressing HKA2, cGMP, the second messenger of ANP, increased the membrane expression, activity, and Na+-transporting rate of HKA2. Feeding mice with a NH4Cl-enriched diet increased urinary excretion of aldosterone and induced a transient Na+ retention that reversed within 3 days. At that time, expression of ANP mRNA in the collecting duct and urinary excretion of cGMP were increased. Reversion of Na+ retention was prevented by treatment with an inhibitor of ANP receptors and was absent in HKA2-null mice. In conclusion, paracrine stimulation of HKA2 by ANP is responsible for the escape of the Na+-retaining effect of aldosterone during metabolic acidosis.

Keywords: H-K-ATPase; aldosterone; atrial natriuretic peptide; cGMP; collecting duct; metabolic acidosis; sodium secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium*
  • Acidosis / enzymology*
  • Acidosis / genetics
  • Acidosis / physiopathology
  • Acidosis / urine
  • Adaptation, Physiological
  • Aldosterone / urine
  • Animals
  • Atrial Natriuretic Factor / metabolism*
  • Cyclic GMP / urine
  • Female
  • H(+)-K(+)-Exchanging ATPase / deficiency
  • H(+)-K(+)-Exchanging ATPase / genetics
  • H(+)-K(+)-Exchanging ATPase / metabolism*
  • Hydrogen-Ion Concentration
  • Kidney Tubules, Collecting / enzymology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Paracrine Communication
  • Rats
  • Signal Transduction
  • Sodium / urine*
  • Xenopus laevis

Substances

  • Aldosterone
  • Atrial Natriuretic Factor
  • Sodium
  • ATP12A protein, mouse
  • H(+)-K(+)-Exchanging ATPase
  • Cyclic GMP