Renal collecting duct nos1 maintains fluid-electrolyte homeostasis and blood pressure

Kelly A. Hyndman, Erika I. Boesen, Ahmed Abdelrazik Elmarakby, Michael W Brands, Paul Huang, Donald E. Kohan, David M. Pollock, Jennifer S. Pollock

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Nitric oxide is a pronatriuretic and prodiuretic factor. The highest renal NO synthase (NOS) activity is found in the inner medullary collecting duct. The collecting duct (CD) is the site of daily fine-tune regulation of sodium balance, and led us to hypothesize that a CD-specific deletion of NOS1 would result in an impaired ability to excrete a sodium load leading to a salt-sensitive blood pressure phenotype. We bred AQP2-CRE mice with NOS1 floxed mice to produce flox control and CD-specific NOS1 knockout (CDNOS1KO) littermates. CDs from CDNOS1KO mice produced 75% less nitrite, and urinary nitrite+nitrate (NOx) excretion was significantly blunted in the knockout genotype. When challenged with high dietary sodium, CDNOS1KO mice showed significantly reduced urine output, sodium, chloride, and NOx excretion, and increased mean arterial pressure relative to flox control mice. In humans, urinary NOx is a newly identified biomarker for the progression of hypertension. These findings reveal that NOS1 in the CD is critical in the regulation of fluid-electrolyte balance, and this new genetic model of CD NOS1 gene deletion will be a valuable tool to study salt-dependent blood pressure mechanisms.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalHypertension
Volume62
Issue number1
DOIs
StatePublished - Jul 1 2013

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Electrolytes
Homeostasis
Water-Electrolyte Balance
Nitrites
Blood Pressure
Kidney
Knockout Mice
Salts
Sodium
Dietary Sodium
Genetic Models
Gene Deletion
Sodium Chloride
Nitric Oxide Synthase
Nitrates
Arterial Pressure
Nitric Oxide
Biomarkers
Genotype
Urine

Keywords

  • NOS1
  • blood pressure
  • collecting duct
  • salt-sensitivity
  • sodium excretion

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Renal collecting duct nos1 maintains fluid-electrolyte homeostasis and blood pressure. / Hyndman, Kelly A.; Boesen, Erika I.; Elmarakby, Ahmed Abdelrazik; Brands, Michael W; Huang, Paul; Kohan, Donald E.; Pollock, David M.; Pollock, Jennifer S.

In: Hypertension, Vol. 62, No. 1, 01.07.2013, p. 91-98.

Research output: Contribution to journalArticle

Hyndman, Kelly A. ; Boesen, Erika I. ; Elmarakby, Ahmed Abdelrazik ; Brands, Michael W ; Huang, Paul ; Kohan, Donald E. ; Pollock, David M. ; Pollock, Jennifer S. / Renal collecting duct nos1 maintains fluid-electrolyte homeostasis and blood pressure. In: Hypertension. 2013 ; Vol. 62, No. 1. pp. 91-98.
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