Document Detail

Role of Rac1 GTPase in salt-sensitive hypertension.
MedLine Citation:
PMID:  23377658     Owner:  NLM     Status:  In-Data-Review    
PURPOSE OF REVIEW: The aldosterone/mineralocorticoid receptor system plays an important role in the long-term blood pressure control through Na homeostasis. Its overactivation has been implicated in salt-sensitive hypertension. Excessive salt intake augments the function of mineralocorticoid receptor, despite lowering circulating aldosterone levels, but the mechanism had long been elusive. Recently, Rac1, a member of Rho family small GTP-binding proteins, has emerged as a novel ligand-independent modulator of mineralocorticoid receptor activity. In this review, the roles of Rac1 in the pathogenesis of salt-sensitive hypertension and kidney injury have been summarized.
RECENT FINDINGS: Genetic engineering studies have highlighted the new aspects of Rac1 and its regulators in salt-sensitive hypertension and cardiac and renal disease. New evidence shows the essential roles of Rac1 in salt-evoked paradoxical mineralocorticoid receptor activation observed in salt-sensitive models and in renal tubular Na reabsorption through reduced nicotinamide-adenine dinucleotide phosphate oxidase-mediated oxidative stress or direct regulation of Na transporters.
SUMMARY: The emerging concept of 'ligand-independent aberrant mineralocorticoid receptor activation by Rac1' in the pathogenesis of salt-sensitive hypertension and kidney injury has been reviewed. Rac inhibition, in addition to mineralocorticoid receptor blockade and salt restriction, would be a new promising strategy for the treatment of salt-sensitive hypertension.
Miki Nagase
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  22     ISSN:  1535-3842     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  148-55     Citation Subset:  IM    
Division of Chronic Kidney Disease, Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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