Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats.
Salt
Tamm Horsfall protein
blood pressure
renal physiology
salt-sensitive hypertension
Journal
Clinical science (London, England : 1979)
ISSN: 1470-8736
Titre abrégé: Clin Sci (Lond)
Pays: England
ID NLM: 7905731
Informations de publication
Date de publication:
22 12 2021
22 12 2021
Historique:
received:
21
10
2021
revised:
24
11
2021
accepted:
06
12
2021
pubmed:
7
12
2021
medline:
4
1
2022
entrez:
6
12
2021
Statut:
ppublish
Résumé
Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension. Normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) (n=8/sex/strain) were maintained on 1% NaCl for 3 weeks. A subset of salt-loaded SHRSP was treated with nifedipine. Salt-loading in SHRSP increased blood pressure (ΔSBP 35 ± 5 mmHg, P<0.0001) and kidney injury markers such as kidney injury marker-1 (KIM-1; fold change, FC 3.4; P=0.003), neutrophil gelatinase-associated lipocalin (NGAL; FC, 2.0; P=0.012) and proteinuria. After salt-loading there was a reduction in urinary UMOD excretion in WKY and SHRSP by 26 and 55% respectively, compared with baseline. Nifedipine treatment reduced blood pressure (BP) in SHRSP, however, did not prevent salt-induced reduction in urinary UMOD excretion. In all experiments, changes in urinary UMOD excretion were dissociated from kidney UMOD protein and mRNA levels. Colocalization and ex-vivo studies showed that salt-loading increased intracellular UMOD retention in both WKY and SHRSP. Our study provides novel insights into the interplay among salt, UMOD, and BP. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.
Identifiants
pubmed: 34870708
pii: 230369
doi: 10.1042/CS20211017
pmc: PMC8689196
doi:
Substances chimiques
Calcium Channel Blockers
0
Sodium Chloride, Dietary
0
Umod protein, rat
0
Uromodulin
0
Nifedipine
I9ZF7L6G2L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2749-2761Subventions
Organisme : British Heart Foundation
ID : RE/13/5/30177
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RE/18/6/34217
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/58/34179
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/40/34477
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/17/63/33485
Pays : United Kingdom
Informations de copyright
© 2021 The Author(s).
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