title: Activation of mineralocorticoid receptor in salt-sensitive hypertension.
abstract: The impaired capacity of the kidney to excrete sodium plays an essential role in the development of hypertension. Adrenal corticosteroids control renal handling of sodium by regulating tubular sodium reabsorption in the distal nephron where both mineralocorticoid receptors (MR) and glucocorticoid receptors are expressed. In addition, cell type- and segment-specific expression of 11β-HSD2 and sodium transporters such as Na-Cl cotransporter (NCC), epithelial sodium channel (ENaC), and pendrin/Na(+)-driven Cl(-)/HCO3 (-) exchanger (NDCBE) builds a distinctive model of sodium transport in the aldosterone-sensitive distal nephron. Aberrant MR activation in the distal nephron triggers salt-sensitive hypertension and hypokalemia through inappropriate sodium reabsorption and potassium secretion. However, MR activity is not necessarily modulated by the ligand alone. Recently, several lines of evidence revealed alternative mechanisms that regulate the activity of MR in a ligand-independent manner or through ligand binding modulation. This review summarizes the disorders related to MR activation in individual tubular cells and highlights the renal mechanism of salt-sensitive hypertension and new approaches for the prevention and treatment of this disease.
authors.affiliation: Department of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ayuzawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000293:injuries / Q000378:metabolism; D008901:Mineralocorticoids / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000378:metabolism*
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary