High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology..
AIMS: High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic-pituitary-adrenal axis activation and leads to sustained glucocorticoid excess.
METHODS AND RESULTS: In male C57BL/6 mice, high salt intake for 2-8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic-pituitary-adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic-pituitary-adrenal axis activation by high salt diet.
CONCLUSION: Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells.
| Errataetall: |
CommentIn: Cardiovasc Res. 2023 Jul 6;119(8):1619-1621. - PMID 37212451 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Cardiovascular research - 119(2023), 8 vom: 06. Juli, Seite 1740-1750 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Costello, Hannah M [VerfasserIn] |
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| Links: |
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| Themen: |
11000-17-2 |
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| Anmerkungen: |
Date Completed 10.07.2023 Date Revised 24.11.2023 published: Print CommentIn: Cardiovasc Res. 2023 Jul 6;119(8):1619-1621. - PMID 37212451 Citation Status MEDLINE |
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| doi: |
10.1093/cvr/cvac160 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348822413 |
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| 100 | 1 | |a Costello, Hannah M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 10.07.2023 | ||
| 500 | |a Date Revised 24.11.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Cardiovasc Res. 2023 Jul 6;119(8):1619-1621. - PMID 37212451 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. | ||
| 520 | |a AIMS: High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic-pituitary-adrenal axis activation and leads to sustained glucocorticoid excess | ||
| 520 | |a METHODS AND RESULTS: In male C57BL/6 mice, high salt intake for 2-8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic-pituitary-adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic-pituitary-adrenal axis activation by high salt diet | ||
| 520 | |a CONCLUSION: Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cortisol | |
| 650 | 4 | |a Glucocorticoid excess | |
| 650 | 4 | |a Glucocorticoid receptor | |
| 650 | 4 | |a Salt | |
| 650 | 4 | |a Stress | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Sodium Chloride, Dietary |2 NLM | |
| 650 | 7 | |a Vasopressins |2 NLM | |
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| 700 | 1 | |a Krilis, Georgios |e verfasserin |4 aut | |
| 700 | 1 | |a Grenier, Celine |e verfasserin |4 aut | |
| 700 | 1 | |a Severs, David |e verfasserin |4 aut | |
| 700 | 1 | |a Czopek, Alicja |e verfasserin |4 aut | |
| 700 | 1 | |a Ivy, Jessica R |e verfasserin |4 aut | |
| 700 | 1 | |a Nixon, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Holmes, Megan C |e verfasserin |4 aut | |
| 700 | 1 | |a Livingstone, Dawn E W |e verfasserin |4 aut | |
| 700 | 1 | |a Hoorn, Ewout J |e verfasserin |4 aut | |
| 700 | 1 | |a Dhaun, Neeraj |e verfasserin |4 aut | |
| 700 | 1 | |a Bailey, Matthew A |e verfasserin |4 aut | |
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