Acute Intravenous NaCl and Volume Expansion Reduces Sodium-Chloride Cotransporter Abundance and Phosphorylation in Urinary Extracellular Vesicles.
NaCl loading
aquaporin 2
extracellular vesicles
hypertension
phosphorylation
primary aldosteronism
salt loading
sodium-chloride cotransporter
volume expansion
Journal
Kidney360
ISSN: 2641-7650
Titre abrégé: Kidney360
Pays: United States
ID NLM: 101766381
Informations de publication
Date de publication:
26 05 2022
26 05 2022
Historique:
received:
18
01
2022
accepted:
28
02
2022
entrez:
21
9
2022
pubmed:
22
9
2022
medline:
24
9
2022
Statut:
epublish
Résumé
Sodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated. We used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 patients with hypertension who had repeatedly raised aldosterone/renin ratios undergoing infusion of 2 L of 0.9% saline over 4 hours. When measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change [FC]=0.70); pendrin (FC=0.84); AQP2 (FC=0.62); and uEV markers, including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52), and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC; FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, whereas the significant decrease in AQP2 persisted (FC=0.62). We conclude that (
Sections du résumé
Background
Sodium chloride (NaCl) loading and volume expansion suppress the renin-angiotensin-aldosterone system to reduce renal tubular reabsorption of NaCl and water, but effects on the sodium-chloride cotransporter (NCC) and relevant renal transmembrane proteins that are responsible for this modulation in humans are less well investigated.
Methods
We used urinary extracellular vesicles (uEVs) as an indirect readout to assess renal transmembrane proteins involved in NaCl and water homeostasis in 44 patients with hypertension who had repeatedly raised aldosterone/renin ratios undergoing infusion of 2 L of 0.9% saline over 4 hours.
Results
When measured by mass spectrometry in 13 patients, significant decreases were observed in NCC (median fold change [FC]=0.70); pendrin (FC=0.84); AQP2 (FC=0.62); and uEV markers, including ALIX (FC=0.65) and TSG101 (FC=0.66). Immunoblotting reproduced the reduction in NCC (FC=0.54), AQP2 (FC=0.42), ALIX (FC=0.52), and TSG101 (FC=0.55) in the remaining 31 patients, and demonstrated a significant decrease in phosphorylated NCC (pNCC; FC=0.49). However, after correction for ALIX, the reductions in NCC (FC=0.90) and pNCC (FC=1.00) were no longer apparent, whereas the significant decrease in AQP2 persisted (FC=0.62).
Conclusion
We conclude that (
Identifiants
pubmed: 36128481
doi: 10.34067/KID.0000362022
pii: 02200512-202205000-00015
pmc: PMC9438418
doi:
Substances chimiques
Aquaporin 2
0
Saline Solution
0
Sodium Chloride Symporters
0
Water
059QF0KO0R
Sodium Chloride
451W47IQ8X
Aldosterone
4964P6T9RB
Renin
EC 3.4.23.15
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
910-921Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Déclaration de conflit d'intérêts
R.A. Fenton reports serving as an associate editor for the American Journal of Physiology - Renal Physiology and is an editorial board member of JASN. P.A. Welling reports having an advisory or leadership role on the renal editorial board of the American Journal of Physiology; receiving honoraria from the American Physiological Society; serving as chair of the finance committee of the American Physiological Society, and as chair of kidney molecular biology and development of the National Institutes of Health (NIH); and receiving research funding from the NIH. All remaining authors have nothing to disclose.
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