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Activation of Mineralocorticoid Receptor in Salt-Sensitive Hypertension

  • Hypertension and the Kidney (RM Carey, Section Editor)
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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.

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Acknowledgments

This work was supported by Japan Society for the Promotion of Science KAKENHI (Grant Number 21229012).

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Nobuhiro Ayuzawa and Toshiro Fujita declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. 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

    Nobuhiro Ayuzawa & Toshiro Fujita

  2. CREST, Japan Science and Technology Agency, 7 Gobancho, Chiyoda-ku, Tokyo, 102-0076, Japan

    Toshiro Fujita

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  1. Nobuhiro Ayuzawa
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Correspondence to Toshiro Fujita.

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Ayuzawa, N., Fujita, T. Activation of Mineralocorticoid Receptor in Salt-Sensitive Hypertension. Curr Hypertens Rep 17, 44 (2015). https://doi.org/10.1007/s11906-015-0552-2

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