Document Detail


AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure.
MedLine Citation:
PMID:  21459331     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypertension affects more than 1.5 billion people worldwide but the precise cause of elevated blood pressure (BP) cannot be determined in most affected individuals. Nonetheless, blockade of the renin-angiotensin system (RAS) lowers BP in the majority of patients with hypertension. Despite its apparent role in hypertension pathogenesis, the key cellular targets of the RAS that control BP have not been clearly identified. Here we demonstrate that RAS actions in the epithelium of the proximal tubule have a critical and nonredundant role in determining the level of BP. Abrogation of AT(1) angiotensin receptor signaling in the proximal tubule alone is sufficient to lower BP, despite intact vascular responses. Elimination of this pathway reduces proximal fluid reabsorption and alters expression of key sodium transporters, modifying pressure-natriuresis and providing substantial protection against hypertension. Thus, effectively targeting epithelial functions of the proximal tubule of the kidney should be a useful therapeutic strategy in hypertension.
Authors:
Susan B Gurley; Anne D M Riquier-Brison; Jurgen Schnermann; Matthew A Sparks; Andrew M Allen; Volker H Haase; John N Snouwaert; Thu H Le; Alicia A McDonough; Beverley H Koller; Thomas M Coffman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell metabolism     Volume:  13     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-04     Completed Date:  2011-07-12     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  469-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology*
Hypertension / pathology
Kidney Tubules, Proximal / metabolism*
Mice
Receptor, Angiotensin, Type 1 / genetics,  metabolism*
Renin-Angiotensin System / drug effects
Signal Transduction
Sodium / metabolism
Sodium-Hydrogen Antiporter / metabolism
Sodium-Potassium-Chloride Symporters / metabolism
Solute Carrier Family 12, Member 1
Grant Support
ID/Acronym/Agency:
2R01 HL056122/HL/NHLBI NIH HHS; DK083785/DK/NIDDK NIH HHS; R01 DK081646/DK/NIDDK NIH HHS; R01 DK083785/DK/NIDDK NIH HHS; R01 HL056122/HL/NHLBI NIH HHS; R01 HL056122-14/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptor, Angiotensin, Type 1; 0/Slc12a1 protein, mouse; 0/Sodium-Hydrogen Antiporter; 0/Sodium-Potassium-Chloride Symporters; 0/Solute Carrier Family 12, Member 1; 0/sodium-hydrogen exchanger 3; 9NEZ333N27/Sodium
Comments/Corrections

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