Document Detail

TASK-3 channel deletion in mice recapitulates low-renin essential hypertension.
MedLine Citation:
PMID:  22493079     Owner:  NLM     Status:  MEDLINE    
Idiopathic primary hyperaldosteronism (IHA) and low-renin essential hypertension (LREH) are common forms of hypertension, characterized by an elevated aldosterone-renin ratio and hypersensitivity to angiotensin II. They are suggested to be 2 states within a disease spectrum that progresses from LREH to IHA as the control of aldosterone production by the renin-angiotensin system is weakened. The mechanism(s) that drives this progression remains unknown. Deletion of Twik-related acid-sensitive K(+) channels (TASK) subunits, TASK-1 and TASK-3, in mice (T1T3KO) produces a model of human IHA. Here, we determine the effect of deleting only TASK-3 (T3KO) on the control of aldosterone production and blood pressure. We find that T3KO mice recapitulate key characteristics of human LREH, salt-sensitive hypertension, mild overproduction of aldosterone, decreased plasma-renin concentration with elevated aldosterone:renin ratio, hypersensitivity to endogenous and exogenous angiotensin II, and failure to suppress aldosterone production with dietary sodium loading. The relative differences in levels of aldosterone output and aldosterone:renin ratio and in autonomy of aldosterone production between T1T3KO and T3KO mice are reminiscent of differences in human hypertensive patients with LREH and IHA. Our studies establish a model of LREH and suggest that loss of TASK channel activity may be one mechanism that advances the syndrome of low renin hypertension.
Nick A Guagliardo; Junlan Yao; Changlong Hu; Elaine M Schertz; David A Tyson; Robert M Carey; Douglas A Bayliss; Paula Q Barrett
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-09
Journal Detail:
Title:  Hypertension     Volume:  59     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-06-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  999-1005     Citation Subset:  IM    
Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, VA 22908, USA.
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MeSH Terms
Aldosterone / metabolism
Angiotensin II / pharmacology
Disease Models, Animal
Gene Expression Regulation
Hyperaldosteronism / genetics*,  physiopathology
Hypertension / genetics*,  physiopathology*
Mice, Inbred C57BL
Mice, Knockout
Potassium Channels / genetics*,  metabolism
Random Allocation
Real-Time Polymerase Chain Reaction
Renin-Angiotensin System / genetics*,  physiology
Sensitivity and Specificity
Sequence Deletion
Sodium / metabolism,  pharmacology
Grant Support
Reg. No./Substance:
0/Potassium Channels; 0/TASK3 protein, mouse; 11128-99-7/Angiotensin II; 52-39-1/Aldosterone; 7440-23-5/Sodium
Erratum In:
Hypertension. 2012 Jun;59(6):e59

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

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