Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport

Nirupama Ramkumar, Deborah Stuart, Elena Mironova, Vladislav Bugay, Shuping Wang, Nikita Abraham, Atsuhiro Ichihara, James D. Stockand, Donald E. Kohan

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 mo of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na+ excretion and investigated the signaling mechanisms by which PRR regulates Na+ balance. No detectable differences in BP were observed between control and PRR KO mice fed normal- or low-Na+ diets. However, compared with controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na+ balance with normal- and low-Na+ intake. PRR KO mice had an attenuated hypertensive response and reduced Na+ retention following angiotensin II (ANG II) infusion. Furthermore, PRR KO mice had significantly lower epithelial Na+ channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT1, ERK1/2, or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na+ wasting and reduces the hypertensive response to ANG II.

Original languageEnglish (US)
Pages (from-to)F186-F194
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Keywords

  • Angiotensin II
  • Blood pressure
  • Prorenin receptor
  • Sodium transport

ASJC Scopus subject areas

  • Physiology
  • Urology

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