Vasopressin/V2 receptor stimulates renin synthesis in the collecting duct

ALEXIS ANTONIO GONZALEZ PARRA, Flavia Cifuentes-Araneda, Cristobal Ibaceta-Gonzalez, Alex Gonzalez-Vergara, Leonardo Zamora, Ricardo Henriquez, Carla B. Rosales, L. Gabriel Navar, Minolfa C. Prieto

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Renin is synthesized in the principal cells of the collecting duct (CD), and its production is increased via cAMP in angiotensin (ANG) II-dependent hypertension, despite suppression of juxtaglomerular (JG) renin. Vasopressin, one of the effector hormones of the renin-angiotensin system (RAS) via the type 2-receptor (V2R), activates the cAMP/PKA/cAMP response element-binding protein (CREB) pathway and aquaporin-2 expression in principal cells of the CD. Accordingly, we hypothesized that activation of V2R increases renin synthesis via PKA/CREB, independently of ANG II type 1 (AT1) receptor activation in CD cells. Desmopressin (DDAVP; 10−6 M), a selective V2R agonist, increased renin mRNA (∼3-fold), prorenin (∼1.5-fold), and renin (∼2-fold) in cell lysates and cell culture media in the M-1 CD cell line. Cotreatment with DDAVP+H89 (PKA inhibitor) or CREB short hairpin (sh) RNA prevented this response. H89 also blunted DDAVP-induced CREB phosphorylation and nuclear localization. In 48-h water-deprived (WD) mice, prorenin-renin protein levels were increased in the renal inner medulla (∼1.4- and 1.8-fold). In WD mice treated with an ACE inhibitor plus AT1 receptor blockade, renin mRNA and prorenin protein levels were still higher than controls, while renin protein content was not changed. In M-1 cells, ANG II or DDAVP increased prorenin-renin protein levels; however, there were no further increases by combined treatment. These results indicate that in the CD the activation of the V2R stimulates renin synthesis via the PKA/CREB pathway independently of RAS, suggesting a critical role for vasopressin in the regulation of renin in the CD.

Original languageEnglish
Pages (from-to)F284-F293
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number4
DOIs
StatePublished - 15 Feb 2016

Keywords

  • Collecting duct
  • Distal tubular renin
  • Intrarenal renin-angiotensin system
  • PKA/CREB
  • Prorenin
  • Water deprivation

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