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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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Cites
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547
STUDIES ON EXPERIMENTAL HYPERTENSION
Goldblatt, H., Lynch, J., Hanzal, R. F., & Summerville, W. W. (1934) · The Journal of Experimental Medicine · doi:10.1084/jem.59.3.347 · Cited by 2,145
The sympathetic control of blood pressure
Guyenet, P. G. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1902 · Cited by 1,863
New roles for astrocytes: redefining the functional architecture of the brain.
Nedergaard, M., Ransom, B., & Goldman, S. A. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.08.008 · Cited by 1,334 · cited 1×
“of the astrocyte surface.(65) Thus, it is possible that AngII may”
BackgroundTouyz, R. M., Chen, X., Tabet, F., Yao, G., He, G., Quinn, M. T., Pagano, P. J., & Schiffrin, E. L. (2002) · Circulation Research · doi:10.1161/01.res.0000020404.01971.2f · Cited by 590
Xiao, L., & Harrison, D. G. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.01.013 · Cited by 557
Remodeling of cerebral arterioles in chronic hypertension.
Baumbach, G. L., & Heistad, D. D. (1989) · Hypertension · doi:10.1161/01.hyp.13.6.968 · Cited by 496
Brain Microglial Cytokines in Neurogenic Hypertension
Shi, P. D., Díez-Freire, C., Jun, J. Y., Qi, Y., Katovich, M. J., Li, Q., Sriramula, S., Francis, J., Sumners, C., & Raizada, M. K. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.150409 · Cited by 384
Savoia, C., & Schiffrin, E. L. (2006) · Current Opinion in Internal Medicine · doi:10.1097/01.mnh.0000203189.57513.76 · Cited by 287
Brain renin–angiotensin system dysfunction in hypertension: recent advances and perspectives
Veerasingham, S. J., & Raizada, M. K. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705262 · Cited by 251
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Zibrila, A. I., Zhou, J., Wang, X., Zeng, M., Ali, M. A., Liu, X., Alkuhali, A. A., Zeng, Z., Meng, Y., Wang, Z., et al. (2024) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-024-03010-2 · Cited by 5
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Perrotta, M., & Carnevale, D. (2024) · The Journal of Physiology · doi:10.1113/jp284078 · Cited by 5
Rodrigues, B., Feriani, D. J., Gambassi, B. B., Irigoyen, M. C., Angelis, K. D., & Coelho‐Júnior, H. J. (2017) · Motriz Revista de Educação Física · doi:10.1590/s1980-6574201700si0005 · Cited by 5
McCaffrey, D., Kostoglou, Y., Tao, A., Chan, R. J., Vardy, J. L., Chan, A., Furlong, T. M., Lawther, A. J., Weickert, C. S., & Walker, A. K. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106205 · Cited by 4
kalsoom, U.-E., Jin, J., Meng, W., Su, Y., Wu, C., & Wu, Q. (2026) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2026.119096 · Cited by 4
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Toumpourleka, M., & Stavrakis, S. (2026) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00541.2025 · Cited by 4
Effects of Goldblatt hypertension on rats’ hippocampal cholinergic system
Sepehri, H., Ganji, F., Nazari, Z., & Vahid, M. (2022) · Translational Neuroscience · doi:10.1515/tnsci-2022-0215 · Cited by 4
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Carnevale, D. (2023) · Current Hypertension Reports · doi:10.1007/s11906-023-01268-y · Cited by 5
Wang, L.-Y., Hu, H., Sheng, Z.-H., Ou, Y., Ou, Y., Guo, F., Zhu, Y.-K., Tan, L., & Initiative, A. D. N. (2025) · Neurotoxicity Research · doi:10.1007/s12640-025-00740-8 · Cited by 5
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Shaikh, N., Chanda, A. H., Nawaz, S., Alkubaisi, A., Alyafei, A., Ganaw, A. E. A., & Malmstrom, M. F. (2021) · Springer eBooks · doi:10.1007/978-3-030-81333-8_1 · Cited by 4
ShamsEldeen, A. M., Fawzy, A. S., Ashour, H., Abdel-Rahman, M. M., Nasr, H. E., Mohammed, L. A., Latif, N. S. A., Mahrous, A. M. K., & Abdelfattah, S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1116705 · Cited by 4
Yokoi, A., Kawada, T., Yokota, S., Kakuuchi, M., Matsushita, H., Nishiura, A., Li, M., Uemura, K., Alexander, J., Tanaka, R., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0286767 · Cited by 4
Calzerra, N. T. M., Gomes, C. F., & de Queiroz, T. M. (2018) · Acta Brasiliensis · doi:10.22571/2526-433876 · Cited by 4
Li, B., Ming, R., & Guo, H. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107691 · Cited by 3
Dinh, Q. N., Lo, C., Zhang, D. E. W., Tran, V., Hughes, T. A. G., Georgia-Sherriff, A., Diep, H., Kim, H. A., Zhang, S. R., Arce, L. J. B., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-52214-0 · Cited by 4
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Singh, G., Maparu, K., & Aran, K. R. (2026) · Metabolic Brain Disease · doi:10.1007/s11011-025-01780-x · Cited by 2
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Chen, J.-L., Ge, R., Li, X., Zhang, Y., Hao, W., Li, N., Xu, Z.-Q., Chen, Q., Li, Y., Zhu, G., et al. (2024) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-024-01034-x · Cited by 2
Yamazato, M., Ishida, A., Yamazato, Y., Nakamura, T., & Ohya, Y. (2018) · Hypertension Research · doi:10.1038/s41440-018-0088-3 · Cited by 2
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Chen, N., CHENG, G., Wei, B., Bi, Q., Lu, C. C., Wang, S., & Shi, P. D. (2022) · Scientia Sinica Vitae · doi:10.1360/ssv-2022-0082 · Cited by 2
Pathophysiology of Cognitive Decline and Dementia in Hypertension
Sierra, C., Armario, P., & Gómez-Choco, M. J. (2024) · Updates in hypertension and cardiovascular protection · doi:10.1007/978-3-031-64928-8_18 · Cited by 1
Hypertension and Intracranial Hypertension Association: A Narrative Review
Correia, M. C., Inuzuka, S., da Costa, M. M., Vitorino, P. V. D. O., Piza, P. V. D. T., Frigieri, G. H., Sousa, A. L. L., Coca, A., & Barroso, W. K. S. (2025) · Current Hypertension Reviews · doi:10.2174/0115734021394152250922224959 · Cited by 2
Noto, N. M., Robison, L. S., & Speth, R. C. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149999 · Cited by 1
Korpal, A. K., Brown, C. H., & Schwenke, D. O. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2128-x · Cited by 1
Badimón, L., Tanner, F. C., Camici, G. G., & Vilahur, G. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780198755777.003.0018 · Cited by 1
Braga, V. A. (2019) · Hypertension Research · doi:10.1038/s41440-019-0230-x · Cited by 1
The Brain Renin−Angiotensin System
de Kloet, A. D., & Krause, E. G. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00063-8
Masson, G. S. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2014.tde-19112014-133201
de Fragas, M. G. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2019.tde-22032019-113127
Elucidating Mechanisms of Neurobehavioral Dysfunction in a Rodent Model of Traumatic Brain Injury
Logsdon, A. F. (2016) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.6106
Calcineurin Inhibitor Use and Myoclonus Association. Is There a Clinical Implication?
Verdiner, R. E., Arroyo, R. C., Chaudhry, M. R., Khurmi, N. S., Poterack, K. A., Gorlin, A., Jayaraman, A., & Rodriguez, G. J. (2021) · Open Journal of Anesthesiology · doi:10.4236/ojanes.2021.114009
Althammer, F., & Stern, J. E. (2021) · Masterclass in neuroendocrinology · doi:10.1007/978-3-030-62383-8_5
Self-citationYouwakim, J., Vallerand, D., & Girouard, H. (2021) · Research Square · doi:10.21203/rs.3.rs-956885/v1
Batool, Y. (2021) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3-x7dx-b041
Microvascular effects of aldosterone and salt in health, obesity and hypertension
Sch�tten (2019) · Research Publications (Maastricht University) · doi:10.26481/dis.20190620ms
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Carlson, S. H., Stocker, S. D., & Wyss, J. M. (2016) · Springer eBooks · doi:10.1007/978-3-319-29152-9_4
Obesity Hypertension: Clinical Aspects
Macumber, I. R., & Flynn, J. T. (2022) · Springer eBooks · doi:10.1007/978-3-319-31420-4_17-2
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Sriramula, S., & Biancardi, V. C. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99618-1.00017-9
Self-citationImpaired oxytocin signaling in the central amygdala in rats with chronic heart failurePreprint
Althammer, F., Roy, R. K., Kirchner, M. K., Campos‐Lira, E., Schimmer, S., Charlet, A., Grinevich, V., & Stern, J. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.22.568271
Self-citationGuo, X., Hongyu, M., Cui, Z., Zhao, Q., Zhang, Y., Jia, L., Zhang, L., Guo, H., Zhang, X., Zhang, Y., et al. (2024) · High Altitude Medicine & Biology · doi:10.1089/ham.2023.0098
Shirah, B. H., zu Eulenburg, P., Overbey, E. G., Kim, J., Burke, M., Hirschberg, J. W., Schulze, I., Ryon, K. A., Proszynski, J., Meydan, C., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-33918-9.00007-9 · Cited by 1
Chronic Treatment of a Mouse Model of Cerebral Amyloid Angiopathy and Brain AT 1 Receptor ExpressionPreprint
Noto, N. M., Robison, L. S., & Speth, R. C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.16.654535 · Cited by 1
Al-Gholam, M. A.-S., Abd-Elhafiz, H. I., & Essawy, A. S. (2025) · Immunopharmacology and Immunotoxicology · doi:10.1080/08923973.2025.2606226
Olschewski, D. N., Nazarzadeh, N., Lange, F., Koenig, A. M., Kulka, C., Abraham, J.-A., Blaschke, S. J., Merkel, R., Hoffmann, B., Fink, G. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26739387
Olschewski, D. N., Nazarzadeh, N., Lange, F., Koenig, A. M., Kulka, C., Abraham, J.-A., Blaschke, S. J., Merkel, R., Hoffmann, B., Fink, G. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26739378
Olschewski, D. N., Nazarzadeh, N., Lange, F., Koenig, A. M., Kulka, C., Abraham, J.-A., Blaschke, S. J., Merkel, R., Hoffmann, B., Fink, G. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26739381
Olschewski, D. N., Nazarzadeh, N., Lange, F., Koenig, A. M., Kulka, C., Abraham, J.-A., Blaschke, S. J., Merkel, R., Hoffmann, B., Fink, G. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26739384
Riganello, F., Cortese, M. D., Vatrano, M., Lucca, L. F., Pugliese, M. E., Ursino, M., Leto, E., Cerasa, A., Schiff, N. D., & Soddu, A. (2025) · Clinical Autonomic Research · doi:10.1007/s10286-025-01175-z
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Podhajsky, G., Marla, K., Marticoff, A. P., Nguyen, K., Kempton, T., Salehpour, S., Duffy, C., & Bennion, D. M. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15020743
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Bastrup, J., Folke, J., Kaalund, S. S., Rasmussen, M., Aznar, S., & Jepps, T. A. (2026) · GeroScience · doi:10.1007/s11357-026-02097-y · Cited by 1
Zhou, J.-J., Shao, J.-Y., Chen, S.-R., Li, D.-P., & Pan, H. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.03.729868
Heart-brain interaction and research progress following traumatic brain injury
Shen, D., Huang, R., Wang, L., Pang, Q., Li, M., & Wang, T. Z. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.07.018
Levesque, P., Canivet, C., Drolet, M., Martel, J., Risbrough, V. B., & Deslauriers, J. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107547
Chen, S. C., Lin, C., Shen, C., Chan, M. W. Y., Chen, Z., Lin, Y.-H., Shi, C., Lin, C.-M., Huang, T. H., Lu, J. C. H., et al. (2026) · Cells · doi:10.3390/cells15171550
Zhou, J.-J., Shao, J.-Y., Chen, S.-R., Li, D., & Pan, H. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107607
Okuda, D. T., Burgess, K. W., Wright, C., Jones-McCreary, M. C., Huddleston, I., Santoyo, J. R., Punnen, T. G., Sguigna, P. V., Tardo, L. M., Lebrun‐Frénay, C., et al. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e01060
Kordas, B., Zglejc‐Waszak, K., Mizia, P., Matuszewski, W., Skowrońska, A., Majewski, M. K., & Juranek, J. K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188375
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Bakkar, N. Z., Ghazi, R., Mougharbil, N., Hammoud, S. H., Sabra, R., Eid, A. H., & EL‐Yazbi, A. F. (2026) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.70363
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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