Journal article
Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway
Scientific reports, Vol.6(1), pp.18360-18360
01/05/2016
DOI: 10.1038/srep18360
PMCID: PMC4700450
PMID: 26728390
Abstract
The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na+)-chloride (Cl-) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK, and WNK4 knockout mice. The quantities of Ncc mRNA, expression of total NCC, phosphorylated (p)-NCC, SPAK and WNK4 in the kidneys as well as NCC inhibition with hydrochlorothiazide and Na+ balance were evaluated. Relative to WT mice, WTA mice had similar levels of Ncc mRNA, but increased expression of total and p-NCC, SPAK, and WNK4 and an exaggerated response to hydrochlorothiazide which could not be observed in SPAK or WNK4 knockout mice with CMA. In WTA mice, increased plasma renin activity, aldosterone and angiotensin II concentrations accompanied by a significantly negative Na+ balance. High Na+ diet abolished the enhanced NCC expression in WTA mice. Furthermore, an angiotensin II type 1 receptor blocker rather than a mineralocorticoid receptor antagonist exerted a marked inhibition on Na+ reabsorption and NCC phosphorylation in WTA mice. CMA increases WNK4-SPAK-dependent NCC phosphorylation and appears to be secondary to previous natriuresis with volume-dependent angiotensin II activation.
Details
- Title: Subtitle
- Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway
- Creators
- Yu-Wei Fang - Shin Kong WHS Memorial HospitalSung-Sen Yang - National Defense Medical CenterChih-Jen Cheng - Tri-Service General HospitalMin-Hua Tseng - Chang Gung Memorial HospitalHui-Min Hsu - Shin Kong WHS Memorial HospitalShih-Hua Lin - National Defense Medical Center
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.6(1), pp.18360-18360
- DOI
- 10.1038/srep18360
- PMID
- 26728390
- PMCID
- PMC4700450
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 10
- Grant note
- SKH-8302-101-DR-08 / Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- Language
- English
- Date published
- 01/05/2016
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984383314102771
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