Document Detail

Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice.
MedLine Citation:
PMID:  24396058     Owner:  NLM     Status:  Publisher    
A network of kinases including WNKs, SPAK, and Sgk1 is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as key hormone to orchestrate these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal, and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride-cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. The renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state changes in K+ intake induce specific molecular and functional changes in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.
Helga Vitzthum; Anika Seniuk; Laura Helene Schulte; Maxie Luise Müller; Hannah Hetz; Heimo Ehmke
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-6
Journal Detail:
Title:  The Journal of physiology     Volume:  -     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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