title: Mechanism of salt-sensitive hypertension: focus on adrenal and sympathetic nervous systems.
abstract: A central role for the kidney among the systems contributing to BP regulation and the development of hypertension has been proposed. Both the aldosterone/mineralocorticoid receptor pathway and the renal sympathetic nervous system have important roles in the regulation of renal excretory function and BP control, but the mechanisms underlying these processes have remained unclear. However, recent studies revealed the activation of two pathways in salt-sensitive hypertension. Notably, Rac1, a member of the Rho-family of small GTP binding proteins, was identified as a novel ligand-independent modulator of mineralocorticoid receptor activity. Furthermore, these studies point to crucial roles for the Rac1-mineralocorticoid receptor-NCC/ENaC and the renal β-adrenergic stimulant-glucocorticoid receptor-WNK4-NCC pathways in certain rodent models of salt-sensitive hypertension. The nuclear mineralocorticoid and glucocorticoid receptors may contribute to impaired renal excretory function and the resulting salt-sensitive hypertension by increasing sodium reabsorption at different tubular segments. This review provides an in-depth discussion of the evidence supporting these conclusions and considers the significance with regard to treating salt-sensitive hypertension and salt-induced cardiorenal injury.
authors.affiliation: Department of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan; and CREST, Tokyo, Japan Toshiro.FUJITA@rcast.u-tokyo.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D006801:Humans; D006977:Hypertension, Renal / Q000378:metabolism* / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects* / Q000493:pharmacokinetics; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D017673:Sodium Chloride, Dietary