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Sex-Specific Cardiovascular Consequences of Long-Term High-Salt Diet in Mice

Duarte, João M N LU orcid ; Sahoglu-Göktas, Sevilay LU ; Vanherle, Lotte LU ; Rafiee, Zeinab LU ; Prakash, Sneha ; Stemmer, Kerstin ; Swärd, Karl LU ; Magnusson, Martin LU orcid and Meissner, Anja LU orcid (2025) In Journal of the American Heart Association
Abstract

BACKGROUND: Excessive dietary salt intake is associated with elevated blood pressure and damage to organs including the heart, vasculature, and kidneys. Women are more prone to salt-sensitive hypertension, yet preclinical studies often focus on men.

METHODS: To examine sex-specific responses to chronic salt loading, male and female C57Bl6/J mice were fed a high-salt diet (HSD; 8% NaCl) from 7 to 14 months of age. Subsets of HSD mice were switched to a normal diet after 28 weeks. Blood pressure was measured via tail-cuff plethysmography, and cardiac function assessed by magnetic resonance imaging. Vascular responses were analyzed by wire myography, and histological and molecular analyses were performed on heart, aorta, and kidney... (More)

BACKGROUND: Excessive dietary salt intake is associated with elevated blood pressure and damage to organs including the heart, vasculature, and kidneys. Women are more prone to salt-sensitive hypertension, yet preclinical studies often focus on men.

METHODS: To examine sex-specific responses to chronic salt loading, male and female C57Bl6/J mice were fed a high-salt diet (HSD; 8% NaCl) from 7 to 14 months of age. Subsets of HSD mice were switched to a normal diet after 28 weeks. Blood pressure was measured via tail-cuff plethysmography, and cardiac function assessed by magnetic resonance imaging. Vascular responses were analyzed by wire myography, and histological and molecular analyses were performed on heart, aorta, and kidney tissues.

RESULTS: After 56 weeks, only HSD-fed females exhibited increased systolic blood pressure (P=0.015), whereas HSD-fed males showed elevated left ventricular stroke volume, end-diastolic volume, and mass (P<0.05). Males displayed aortic remodeling with increased wall thickness and synthetic smooth muscle marker expression. Mesenteric arteries had impaired contractile responses in males, whereas α1-adrenergic tone was elevated in HSD-fed females. Despite no overt renal injury, renal vascular thickening was observed in HSD males and glomerulosclerosis in normal diet females. Diet reversal normalized blood pressure in females and reversed cardiac changes in males.

CONCLUSIONS: Chronic high salt intake leads to distinct sex-specific cardiovascular remodeling in mice. Importantly, diet reversal mitigates these effects, highlighting the potential of dietary interventions in salt-sensitive cardiovascular risk.

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organization
publishing date
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Contribution to journal
publication status
epub
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in
Journal of the American Heart Association
article number
e041945
publisher
Wiley-Blackwell
external identifiers
  • pmid:41070523
ISSN
2047-9980
DOI
10.1161/JAHA.125.041945
language
English
LU publication?
yes
id
d3fc9f71-a9c5-4519-829b-a6b858bda629
date added to LUP
2025-10-10 15:17:20
date last changed
2025-10-10 15:23:03
@article{d3fc9f71-a9c5-4519-829b-a6b858bda629,
  abstract     = {{<p>BACKGROUND: Excessive dietary salt intake is associated with elevated blood pressure and damage to organs including the heart, vasculature, and kidneys. Women are more prone to salt-sensitive hypertension, yet preclinical studies often focus on men.</p><p>METHODS: To examine sex-specific responses to chronic salt loading, male and female C57Bl6/J mice were fed a high-salt diet (HSD; 8% NaCl) from 7 to 14 months of age. Subsets of HSD mice were switched to a normal diet after 28 weeks. Blood pressure was measured via tail-cuff plethysmography, and cardiac function assessed by magnetic resonance imaging. Vascular responses were analyzed by wire myography, and histological and molecular analyses were performed on heart, aorta, and kidney tissues.</p><p>RESULTS: After 56 weeks, only HSD-fed females exhibited increased systolic blood pressure (P=0.015), whereas HSD-fed males showed elevated left ventricular stroke volume, end-diastolic volume, and mass (P&lt;0.05). Males displayed aortic remodeling with increased wall thickness and synthetic smooth muscle marker expression. Mesenteric arteries had impaired contractile responses in males, whereas α1-adrenergic tone was elevated in HSD-fed females. Despite no overt renal injury, renal vascular thickening was observed in HSD males and glomerulosclerosis in normal diet females. Diet reversal normalized blood pressure in females and reversed cardiac changes in males.</p><p>CONCLUSIONS: Chronic high salt intake leads to distinct sex-specific cardiovascular remodeling in mice. Importantly, diet reversal mitigates these effects, highlighting the potential of dietary interventions in salt-sensitive cardiovascular risk.</p>}},
  author       = {{Duarte, João M N and Sahoglu-Göktas, Sevilay and Vanherle, Lotte and Rafiee, Zeinab and Prakash, Sneha and Stemmer, Kerstin and Swärd, Karl and Magnusson, Martin and Meissner, Anja}},
  issn         = {{2047-9980}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Sex-Specific Cardiovascular Consequences of Long-Term High-Salt Diet in Mice}},
  url          = {{http://dx.doi.org/10.1161/JAHA.125.041945}},
  doi          = {{10.1161/JAHA.125.041945}},
  year         = {{2025}},
}