Obese Male Mice Exposed to Early Life Stress Display Sympathetic Activation and Hypertension Independent of Circulating Angiotensin II
BACKGROUND: We have previously reported that male mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show sympathetic activation and increased blood pressure in response to a chronic high-fat diet. The goal of this study was to investigate the contribution of the renin-angiotensin-aldosterone system to the mechanism by which MSEW increases blood pressure and vasomotor sympathetic tone in obese male mice.
METHODS AND RESULTS: Mice were exposed to MSEW during postnatal life. Undisturbed litters served as controls. At weaning, both control and MSEW offspring were placed on a low-fat diet or a high-fat diet for 20 weeks. Angiotensin peptides in serum were similar in control and MSEW mice regardless of the diet. However, a high-fat diet induced a similar increase in angiotensinogen levels in serum, renal cortex, liver, and fat in both control and MSEW mice. No evidence of renin-angiotensin system activation was found in adipose tissue and renal cortex. After chronic treatment with enalapril (2.5 mg/kg per day, drinking water, 7 days), an angiotensin-converting enzyme inhibitor that does not cross the blood-brain barrier, induced a similar reduction in blood pressure in both groups, while the vasomotor sympathetic tone remained increased in obese MSEW mice. In addition, acute boluses of angiotensin II (1, 10, 50 μg/kg s.c.) exerted a similar pressor response in MSEW and control mice before and after enalapril treatment.
CONCLUSIONS: Overall, elevated blood pressure and vasomotor sympathetic tone remained exacerbated in MSEW mice compared with controls after the peripheral inhibition of angiotensin-converting enzyme, suggesting a mechanism independent of angiotensin II.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Journal of the American Heart Association - 13(2024), 1 vom: 02. Jan., Seite e029511 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dalmasso, Carolina [VerfasserIn] |
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| Links: |
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| Themen: |
11128-99-7 |
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| Anmerkungen: |
Date Completed 04.01.2024 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1161/JAHA.123.029511 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a BACKGROUND: We have previously reported that male mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show sympathetic activation and increased blood pressure in response to a chronic high-fat diet. The goal of this study was to investigate the contribution of the renin-angiotensin-aldosterone system to the mechanism by which MSEW increases blood pressure and vasomotor sympathetic tone in obese male mice | ||
| 520 | |a METHODS AND RESULTS: Mice were exposed to MSEW during postnatal life. Undisturbed litters served as controls. At weaning, both control and MSEW offspring were placed on a low-fat diet or a high-fat diet for 20 weeks. Angiotensin peptides in serum were similar in control and MSEW mice regardless of the diet. However, a high-fat diet induced a similar increase in angiotensinogen levels in serum, renal cortex, liver, and fat in both control and MSEW mice. No evidence of renin-angiotensin system activation was found in adipose tissue and renal cortex. After chronic treatment with enalapril (2.5 mg/kg per day, drinking water, 7 days), an angiotensin-converting enzyme inhibitor that does not cross the blood-brain barrier, induced a similar reduction in blood pressure in both groups, while the vasomotor sympathetic tone remained increased in obese MSEW mice. In addition, acute boluses of angiotensin II (1, 10, 50 μg/kg s.c.) exerted a similar pressor response in MSEW and control mice before and after enalapril treatment | ||
| 520 | |a CONCLUSIONS: Overall, elevated blood pressure and vasomotor sympathetic tone remained exacerbated in MSEW mice compared with controls after the peripheral inhibition of angiotensin-converting enzyme, suggesting a mechanism independent of angiotensin II | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a adipose tissue | |
| 650 | 4 | |a hypertension | |
| 650 | 4 | |a maternal separation | |
| 650 | 4 | |a obesity | |
| 650 | 4 | |a renin–angiotensin system | |
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| 700 | 1 | |a Ahmed, Nermin S |e verfasserin |4 aut | |
| 700 | 1 | |a Ghuneim, Sundus |e verfasserin |4 aut | |
| 700 | 1 | |a Cincinelli, Cole |e verfasserin |4 aut | |
| 700 | 1 | |a Leachman, Jaqueline R |e verfasserin |4 aut | |
| 700 | 1 | |a Giani, Jorge F |e verfasserin |4 aut | |
| 700 | 1 | |a Cassis, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Loria, Analia S |e verfasserin |4 aut | |
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