High salt induces early metabolic and extracellular matrix remodeling in Dahl salt-sensitive rats that persists despite subdepressor ACE inhibition
Abstract
Excess salt is a major contributor to hypertension and hypertensive kidney injury, yet the early molecular events linking salt exposure to kidney damage remain incompletely understood. The Dahl salt-sensitive rat is a well-established model of salt-induced hypertension, but early metabolic and transcriptional remodeling in the kidney has not been fully characterized. We investigated early kidney alterations in 35 Dahl salt-sensitive rats fed a high-sodium (HSD) or low-sodium diet (LSD). A subgroup of HSD-fed rats received the ACE inhibitor imidapril at a subdepressor dose (1 mg/kg/day) to examine blood pressure-independent effects. Kidney tissue from 12-week-old animals was analyzed using histology, electron microscopy, transcriptomics, metabolomics, and angiotensin peptide profiling. HSD-fed rats developed hypertension by week 9 and showed kidney remodeling by week 12, including metabolic and transcriptional alterations suggestive of disrupted tricarboxylic acid cycle activity and impaired oxidative phosphorylation in the absence of overt fibrosis. Intra-kidney angiotensin I, II, and angiotensin 1–7 levels were reduced under HSD. Subdepressor ACE inhibition did not significantly alter blood pressure, kidney injury, angiotensin peptide levels, or the transcriptional and metabolic alterations observed in HSD-fed animals. These findings indicate that high salt intake induces early metabolic and extracellular matrix remodeling that is not modified by subdepressor ACE inhibition.
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BibTeX
@article{schuller2026high,
title = {{High salt induces early metabolic and extracellular matrix remodeling in Dahl salt-sensitive rats that persists despite subdepressor ACE inhibition}},
author = {Max Schuller and Mara Kiessling and Juergen Gindlhuber and Konstantin A. Klötzer and Julia Voglhuber and Marion Pollheimer and Corinna Schabhüttl and Dagmar Kolb and Kerstin Hingerl and Hansjörg Habisch and Tobias Madl and Senka Ljubojevic-Holzer and Kathrin Eller},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-77199-w},
url = {https://www.nature.com/articles/s41598-026-77199-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High salt induces early metabolic and extracellular matrix remodeling in Dahl salt-sensitive rats that persists despite subdepressor ACE inhibition
AU - Max Schuller
AU - Mara Kiessling
AU - Juergen Gindlhuber
AU - Konstantin A. Klötzer
AU - Julia Voglhuber
AU - Marion Pollheimer
AU - Corinna Schabhüttl
AU - Dagmar Kolb
AU - Kerstin Hingerl
AU - Hansjörg Habisch
AU - Tobias Madl
AU - Senka Ljubojevic-Holzer
AU - Kathrin Eller
PY - 2026
DA - 2026/10/28
JO - Scientific Reports
DO - 10.1038/s41598-026-77199-w
UR - https://www.nature.com/articles/s41598-026-77199-w
AB - Excess salt is a major contributor to hypertension and hypertensive kidney injury, yet the early molecular events linking salt exposure to kidney damage remain incompletely understood. The Dahl salt-sensitive rat is a well-established model of salt-induced hypertension, but early metabolic and transcriptional remodeling in the kidney has not been fully characterized. We investigated early kidney alterations in 35 Dahl salt-sensitive rats fed a high-sodium (HSD) or low-sodium diet (LSD). A subgroup of HSD-fed rats received the ACE inhibitor imidapril at a subdepressor dose (1 mg/kg/day) to examine blood pressure-independent effects. Kidney tissue from 12-week-old animals was analyzed using histology, electron microscopy, transcriptomics, metabolomics, and angiotensin peptide profiling. HSD-fed rats developed hypertension by week 9 and showed kidney remodeling by week 12, including metabolic and transcriptional alterations suggestive of disrupted tricarboxylic acid cycle activity and impaired oxidative phosphorylation in the absence of overt fibrosis. Intra-kidney angiotensin I, II, and angiotensin 1–7 levels were reduced under HSD. Subdepressor ACE inhibition did not significantly alter blood pressure, kidney injury, angiotensin peptide levels, or the transcriptional and metabolic alterations observed in HSD-fed animals. These findings indicate that high salt intake induces early metabolic and extracellular matrix remodeling that is not modified by subdepressor ACE inhibition.
SN - 2045-2322
ER -