In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance.

Abstract

Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1-related, proline alanine-rich kinase (SPAK) in human urinary exosomes. We isolated exosomes from daily urine samples in 25 patients undergoing fludrocortisone suppression testing (100 μg every 6 hours for 4 days) to diagnose or exclude primary aldosteronism. Over the course of the test, NCC levels increased 3.68-fold (P<0.01) and pNCC levels increased 2.73-fold (P<0.01) relative to baseline. The ratio of pNCC/NCC dropped by 48% (P<0.01). The abundance of WNK4 increased 3.23-fold (P<0.01), but SPAK abundance did not change significantly (P=0.14). Plasma potassium concentration strongly and negatively correlated with pNCC, NCC, and WNK4 abundance (P<0.001 for all). This study shows that, in humans, mineralocorticoid administration is associated with a rapid increase in abundance of NCC and pNCC, possibly via the WNK pathway. These effects may be driven by changes in plasma potassium.

• Authors: Martin J Wolley, Aihua Wu, Shengxin Xu, Richard D Gordon, Robert A Fenton, Michael Stowasser
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 28 Issue 1 Pg. 56-63 (Jan 2017) ISSN: 1533-3450 [Electronic] United States
• PMID: 27381844 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 by the American Society of Nephrology.

Chemical References

• Mineralocorticoids
• Sodium Chloride Symporters

Topics

• Exosomes (metabolism)
• Female
• Humans
• Hyperaldosteronism (metabolism)
• Male
• Middle Aged
• Mineralocorticoids (metabolism)
• Sodium Chloride Symporters (physiology)