Relationships among endogenous ouabain, α-adducin polymorphisms and renal sodium handling in primary hypertension

Paolo Manunta, Marc Maillard, Cristina Tantardini, Marco Simonini, Chiara Lanzani, Lorena Citterio, Paola Stella, Nunzia Casamassima, Michel Burnier, John M. Hamlyn, Giuseppe Bianchi

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: The basolateral Na pump drives renotubular reabsorption. In cultured renal cells, mutant adducins, as well as sub-nanomolar ouabain concentrations, stimulate the Na-K pump. METHODS: To determine whether these factors interact and affect Na handling and blood pressure (BP) in vivo, we studied 155 untreated hypertensive patients subdivided on the basis of their plasma endogenous ouabain or α-adducin genotype (ADD1 Gly460Trp-rs4961). RESULTS: Under basal conditions, proximal tubular reabsorption and plasma Na were higher in patients with mutated Trp ADD1 or increased endogenous ouabain (P = 0.002 and 0.05, respectively). BPs were higher in the high plasma endogenous ouabain group (P = 0.001). Following volume loading, the increment in BP (7.73 vs. 4.81 mmHg) and the slopes of the relationship between BP and Na excretion were greater [0.017 ± 0.002 vs. 0.009 ± 0.003 mmHg/(μEq min)] in ADD1 Trp vs. ADD1 Gly carriers (P <0.05). BP changes were similar, whereas the slopes of the relationship between BP and Na excretion were lower [0.016 ± 0.003 vs. 0.008 ± 0.002 mmHg/(μEq min)] in patients with low vs. high endogenous ouabain (P <0.05). In patients with high endogenous ouabain, volume loading increased the BP in the ADD1 Trp group but not in the Gly group (P <0.05). Thus, patients with ADD1 Trp alleles are sensitive to salt and tubular Na reabsorption remains elevated after volume expansion. CONCLUSION: With saline loading, BP changes are similar in high and low endogenous ouabain patients, whereas tubular Na reabsorption increases in the high endogenous ouabain group. Saline loading unmasks differences in renal Na handling in patients with mutant adducin or high endogenous ouabain and exposes an interaction of endogenous ouabain and Trp alleles on BP.

Original languageEnglish
Pages (from-to)914-920
Number of pages7
JournalJournal of Hypertension
Volume26
Issue number5
DOIs
Publication statusPublished - May 2008

Keywords

  • Functional genomic
  • High blood pressure
  • Na pump inhibitors
  • Na transport
  • Ouabain-like

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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