The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Circulating Angiotensin II Gains Access to the Hypothalamus and Brain Stem During Hypertension via Breakdown of the Blood–Brain Barrier
Open accessAbstract
Angiotensin II–mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood–brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II–mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.
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“Subsequent studies with more moderate and long-lasting increases in BP or in models of chronic hypertension demonstrated in some cases regional ANGII-dependent increases in BBB permeability (e.g., ref. 55), but it remained unclear whether ANGII itself was able to cross the BBB in slow pressor ANGII hypertension.”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [55]
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“of the astrocyte surface.(65) Thus, it is possible that AngII may”
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Brain Microglial Cytokines in Neurogenic Hypertension
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Brain renin–angiotensin system dysfunction in hypertension: recent advances and perspectives
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Faraco, G., Sugiyama, Y., Lane, D., Garcia-Bonilla, L., Chang, H., Santisteban, M. M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86950 · Cited by 350
Hypertension, Neurovascular Dysfunction, and Cognitive Impairment
Santisteban, M. M., Iadecola, C., & Carnevale, D. (2022) · Hypertension · doi:10.1161/hypertensionaha.122.18085 · Cited by 317
Astrocytes are necessary for blood–brain barrier maintenance in the adult mouse brain
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Metadata
- Authors
- Biancardi, V. C., Son, S. J., Ahmadi, S., Filosa, J. A., & Stern, J. E.
- Affiliations
- Augusta University (US)
- Venue
- Hypertension
- Published
- 2014-03
- Volume
- 63
- Issue
- 3
- Pages
- 572-579
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC4080808
- OpenAlex
- W2117536760
- Cited by
- 270
- References
- 73
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 29 · 2023: 20 · 2022: 18 · 2021: 28 · 2020: 22 · 2019: 28 · 2018: 20 · 2017: 22 · 2016: 18 · 2015: 21 · 2014: 9
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL089067, R01HL112225, HL112225)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- angiotensin II, blood-brain barrier permeability, neurogenic hypertension, hypothalamus, paraventricular nucleus, nucleus tractus solitarius, rostral ventrolateral medulla, losartan, angiotensin II type 1 receptor, hydralazine, microglia, neurohumoral regulation, spontaneously hypertensive rats, neuroinflammation
- MeSH terms
- Angiotensin II, Animals, Blood Pressure, Blood-Brain Barrier, Brain Stem, Disease Models, Animal, Hypertension, Hypothalamus, Male, Rats, Inbred SHR, Rats, Inbred WKY, Rats, Wistar, Rats
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