title: Role of Rac1 GTPase in salt-sensitive hypertension.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Chronic Kidney Disease, Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. mnagase-tky@umin.ac.jp
authors: Miki
authors: M
authors: Nagase
mesh_terms: D000818:Animals; D001794:Blood Pressure; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008024:Ligands; D051381:Rats; D020303:Rats, Inbred Dahl; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D008024:Ligands; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D020830:rac1 GTP-Binding Protein