Early life stress enhances angiotensin II-mediated vasoconstriction by reduced endothelial nitric oxide buffering capacity
Open accessAbstract
We reported previously that maternal separation (MS) sensitizes adult rats to angiotensin II (Ang II)–induced hypertension. The aim of this study was to investigate the vascular reactivity to Ang II and the role of renin-angiotensin system components, reactive oxygen species production, and NO synthase (NOS) buffering capacity mediating the exacerbated Ang II–induced responses. MS rats were separated from their mothers for 3 h/d from days 2 to 14 of life. Controls were nonhandled littermates. At 12 weeks of age, aortic Ang II–induced constriction was greater from MS rats compared with controls ( P <0.05); moreover, endothelial denudation abolished this difference. The response to other constrictors was unchanged. Angiotensin type 2 receptor function was reduced in aortic Ang II–induced constriction from MS rats compared with controls. Angiotensin type 1 receptor function was similarly abolished in both groups. However, protein expressions of angiotensin type 1 and angiotensin type 2 receptors were similar in aortic rings from MS and control rats. Preincubation with superoxide inhibitor or scavenger attenuated the Ang II–induced vasoconstriction in control but not in MS rats. However, acute preincubation with an NOS inhibitor enhanced aortic Ang II–induced constriction in aorta from control rats, but this effect was significantly reduced in MS rats compared with control rats. Accordingly, a further increase in Ang II–induced hypertension attributed to chronic NOS inhibition (days 10 to 13) was blunted in MS rats compared with control rats. Similar NOS expression and activity were observed in control and MS rats. In conclusion, MS induces a phenotype with reduced endothelial NOS buffering capacity leading to dysfunctional endothelial Ang II–mediated signaling and sensitization to Ang II–induced vasoconstriction.
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Animal findings suggest that ELS/CT-related significant endothelial dysfunction is linked to reduced endothelial nitrous oxide system buffering capacity with dysfunctional endothelial Angiotensin II-mediated signaling and sensitization to Angiotensin II-induced vasoconstriction.
“and reduced endothelial nitrous oxide system buffering capacity with dysfunctional endothelial Angiotensin II-mediated signaling and sensitization to Angiotensin II-induced vasoconstriction (276).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [276]
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Self-citation
- Authors
- Loria, A. S., Kang, K.-T., Pollock, D. M., & Pollock, J. S.
- Affiliations
- Augusta University (US)
- Venue
- Hypertension
- Published
- 2011-10
- Volume
- 58
- Issue
- 4
- Pages
- 619-626
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3754790
- OpenAlex
- W2144760654
- Semantic Scholar
- b92214fcab7fb507cf4e4bdb9874642c7636494c
- Cited by
- 48
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 7 · 2013: 4 · 2012: 4
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL095499, P01HL069999, R01HL060653)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- early life stress, maternal separation, angiotensin II, vasoconstriction, endothelial nitric oxide, nitric oxide synthase, angiotensin II type 1 receptor, angiotensin II type 2 receptor, reactive oxygen species, superoxide, endothelial dysfunction, renin-angiotensin system, aorta
- MeSH terms
- Angiotensin II, Animals, Animals, Newborn, Aorta, Thoracic, Disease Models, Animal, Endothelium, Vascular, Enzyme Inhibitors, Hypertension, Male, Maternal Deprivation, Rats, Inbred WKY, Stress, Physiological, Vasoconstriction, Signal Transduction, Reactive Oxygen Species, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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