| Role of Rac1 GTPase in salt-sensitive hypertension. | |
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MedLine Citation:
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PMID: 23377658 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Miki Nagase |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Current opinion in nephrology and hypertension Volume: 22 ISSN: 1535-3842 ISO Abbreviation: Curr. Opin. Nephrol. Hypertens. Publication Date: 2013 Mar |
Date Detail:
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Created Date: 2013-02-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9303753 Medline TA: Curr Opin Nephrol Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 148-55 Citation Subset: IM |
Affiliation:
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Division of Chronic Kidney Disease, Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. |
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