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    
Abstract/OtherAbstract:
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.
Authors:
Helga Vitzthum; Anika Seniuk; Laura Helene Schulte; Maxie Luise Müller; Hannah Hetz; Heimo Ehmke
Related Documents :
24505458 - Long-term effects of maternal diabetes on blood pressure and renal function in rat male...
11510748 - The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in japanese but doe...
10976548 - Transdermal nicotine mimics the smoking-induced endothelial dysfunction.
9347078 - Hormonal (acth, cortisol, beta-endorphin, and met-enkephalin) and cardiovascular respon...
4068738 - Intramyocardial pressure in the canine heart. an experimental study.
1737258 - Urethral stress relaxation phenomenon in healthy and stress incontinent women.
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:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Resting pulmonary haemodynamics and shunting: a comparison of sea-level inhabitants to high altitude...
Next Document:  Integrative regulation of human brain blood flow.