Dysregulation of Aldosterone Secretion in Mast Cell-Deficient Mice

Hypertension. 2017 Dec;70(6):1256-1263. doi: 10.1161/HYPERTENSIONAHA.117.09746. Epub 2017 Oct 30.

Abstract

Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell-deficient C57BL/6 KitW-sh/W-sh mice in comparison with wild-type C57BL/6 mice. KitW-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 KitW-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction.

Keywords: adrenal; hyperaldosteronism; hypertension; low-sodium diet; mast cells; mice; renin–angiotensin system.

MeSH terms

  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / pathology
  • Adrenocortical Adenoma / metabolism
  • Adrenocortical Adenoma / pathology
  • Aldosterone / metabolism*
  • Animals
  • Diet, Sodium-Restricted
  • Female
  • Hyperaldosteronism / etiology
  • Hyperaldosteronism / metabolism*
  • Hyperaldosteronism / pathology
  • Male
  • Mast Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms, Experimental*
  • Renin / metabolism

Substances

  • Aldosterone
  • Renin