Overexpression of the sodium chloride cotransporter is not sufficient to cause familial hyperkalemic hypertension

James (Jim) McCormick, Joshua H. Nelson, Chao-Ling Yang, Joshua N. Curry, David Ellison

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The sodium chloride cotransporter (NCC) is the primary target of thiazides diuretics, drugs used commonly for long-term hypertension therapy. Thiazides also completely reverse the signs of familial hyperkalemic hypertension (FHHt), suggesting that the primary defect in FHHt is increased NCC activity. To test whether increased NCC abundance alone is sufficient to generate the FHHt phenotype, we generated NCC transgenic mice; surprisingly, these mice did not display an FHHt-like phenotype. Systolic blood pressures of NCC transgenic mice did not differ from those of wild-type mice, even after dietary salt loading. NCC transgenic mice also did not display hyperkalemia or hypercalciuria, even when challenged with dietary electrolyte manipulation. Administration of fludrocortisone to NCC transgenic mice, to stimulate NCC, resulted in an increase in systolic blood pressure equivalent to that of wild-type mice (approximately 20 mm Hg). Although total NCC abundance was increased in the transgenic animals, phosphorylated (activated) NCC was not, suggesting that the defect in FHHt involves either activation of ion transport pathways other than NCC, or else direct activation of NCC, in addition to an increase in NCC abundance.

Original languageEnglish (US)
Pages (from-to)888-894
Number of pages7
JournalHypertension
Volume58
Issue number5
DOIs
Publication statusPublished - Nov 2011

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Keywords

  • Hyperkalemia
  • Hypertension
  • Mice
  • Sodium chloride symporters
  • Thiazides
  • Transgenic

ASJC Scopus subject areas

  • Internal Medicine

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