CGMP-dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment

Lorena Citterio, Mara Ferrandi, Simona Delli Carpini, Marco Simonini, Tatiana Kuznetsova, Isabella Molinari, Giacomo Dell'Antonio, Chiara Lanzani, Lino Merlino, Elena Brioni, Jan A. Staessen, Giuseppe Bianchi, Paolo Manunta

Research output: Contribution to journalArticle

Abstract

Defective pressure-natriuresis related to abnormalities in the natriuretic response has been associated with hypertension development. A major signaling pathway mediating pressure natriuresis involves the cGMP-dependent protein kinase 1 (PRKG1) that, once activated by Src kinase, inhibits renal Na + reabsorption via a direct action on basolateral Na-K ATPase and luminal Na-H exchanger type 3, as shown in renal tubuli of animals. Because a clear implication of PRKG1 in humans is still lacking, here we addressed whether PRKG1 polymorphisms affect pressurenatriuresis in patients. Naive hypertensive patients (n=574), genotyped for PRKG1 rs1904694, rs7897633, and rs7905063 single nucleotide polymorphisms (SNPs), underwent an acute Na+ loading, and the slope of the pressure-natriuresis relationship between blood pressure and Na+ excretion was calculated. The underlying molecular mechanism was investigated by immunoblotting protein quantifications in human kidneys. The results demonstrate that the PRKG1 risk haplotype GAT (rs1904694, rs7897633, rs7905063, respectively) associates with a rightward shift of the pressure-natriuresis curve (0.017±0.004 μEq/mm Hg per minute) compared with the ACC (0.0013±0.003 μEq/mm Hg per minute; P=0.001). In human kidneys, a positive correlation of protein expression levels between PRKG1 and Src (r=0.83; P+ reabsorption, suggestive of a blunt pressure-natriuresis response.

Original languageEnglish
Pages (from-to)1027-1033
Number of pages7
JournalHypertension
Volume62
Issue number6
DOIs
Publication statusPublished - 2013

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Keywords

  • Human
  • Kidney
  • Natriuresis
  • Pressure-natriuresis
  • Prkg1 protein
  • Salt-sensitive hypertension
  • Sodium reabsorption

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

Citterio, L., Ferrandi, M., Delli Carpini, S., Simonini, M., Kuznetsova, T., Molinari, I., Dell'Antonio, G., Lanzani, C., Merlino, L., Brioni, E., Staessen, J. A., Bianchi, G., & Manunta, P. (2013). CGMP-dependent protein kinase 1 polymorphisms underlie renal sodium handling impairment. Hypertension, 62(6), 1027-1033. https://doi.org/10.1161/HYPERTENSIONAHA.113.01628