Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

de Kloet, Annette D.; Liu, Meng; Rodríguez, Vermalí; Krause, Eric G.; Sumners, Colin

doi:10.1152/ajpregu.00078.2015

Cited by 64Renin-Angiotensin System StudiesHeart Rate Variability and Autonomic ControlEicosanoids and Hypertension Pharmacology

Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

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de Kloet, Annette D., Liu, Meng, Rodríguez, Vermalí, Krause, Eric G., Sumners, Colin·2015·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

DOI 10.1152/ajpregu.00078.2015PMC PMC4591381

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Abstract

Despite tremendous research efforts, hypertension remains an epidemic health concern, leading often to the development of cardiovascular disease. It is well established that in many instances, the brain plays an important role in the onset and progression of hypertension via activation of the sympathetic nervous system. Further, the activity of the renin-angiotensin system (RAS) and of glial cell-mediated proinflammatory processes have independently been linked to this neural control and are, as a consequence, both attractive targets for the development of antihypertensive therapeutics. Although it is clear that the predominant effector peptide of the RAS, ANG II, activates its type-1 receptor on neurons to mediate some of its hypertensive actions, additional nuances of this brain RAS control of blood pressure are constantly being uncovered. One of these complexities is that the RAS is now thought to impact cardiovascular control, in part, via facilitating a glial cell-dependent proinflammatory milieu within cardiovascular control centers. Another complexity is that the newly characterized antihypertensive limbs of the RAS are now recognized to, in many cases, antagonize the prohypertensive ANG II type 1 receptor (AT 1 R)-mediated effects. That being said, the mechanism by which the RAS, glia, and neurons interact to regulate blood pressure is an active area of ongoing research. Here, we review the current understanding of these interactions and present a hypothetical model of how these exchanges may ultimately regulate cardiovascular function.

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The central renin-angiotensin system has an important role in mediating neuroinflammation.
“and the central renin-angiotensin system has an important role in mediating neuroinflammation174.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [174]

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Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology
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<p>Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice</p>
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Angiotensin II and the Cardiac Parasympathetic Nervous System in Hypertension
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Neural Control of Blood Pressure in Chronic Intermittent Hypoxia
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Role of angiotensin-converting enzyme in myeloid cell immune responses
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Angiotensin II Type 1a Receptors in the Subfornical Organ Modulate Neuroinflammation in the Hypothalamic Paraventricular Nucleus in Heart Failure Rats
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The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury
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A Single Angiotensin II Hypertensive Stimulus Is Associated with Prolonged Neuronal and Immune System Activation in Wistar-Kyoto Rats
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Angiotensin type 1a receptors in the paraventricular nucleus of the hypothalamus control cardiovascular reactivity and anxiety-like behavior in male mice
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Angiotensin II–Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats
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Elevated bone marrow sympathetic drive precedes systemic inflammation in angiotensin II hypertension
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Soluble ANPEP Released From Human Astrocytes as a Positive Regulator of Microglial Activation and Neuroinflammation: Brain Renin–Angiotensin System in Astrocyte–Microglia Crosstalk
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Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder
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Nesfatin-1: a new energy-regulating peptide with pleiotropic functions. Implications at cardiovascular level
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Potential mechanisms of hypothalamic renin-angiotensin system activation by leptin and DOCA-salt for the control of resting metabolism
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Physiological and pathophysiological roles of hypothalamic astrocytes in metabolism
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Neuroinflammatory mechanisms of hypertension
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Transcriptomic Analysis of Mouse Brain After Traumatic Brain Injury Reveals That the Angiotensin Receptor Blocker Candesartan Acts Through Novel Pathways
Attilio, P. J., Snapper, D. M., Rusnak, M., Isaac, A. J., Soltis, A. R., Wilkerson, M. D., Dalgard, C. L., & Symes, A. J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.636259 · Cited by 25 · see citing works
Importance of the commissural nucleus of the solitary tract in renovascular hypertension
Melo, M. R., Gasparini, S., Speretta, G. F. F., da Silva, E. F., Pedrino, G. R., Menani, J. V., Zoccal, D. B., Colombari, D. S. A., & Colombari, E. (2019) · Hypertension Research · doi:10.1038/s41440-018-0190-6 · Cited by 25 · see citing works
R1 autonomic nervous system in acute kidney injury
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Astrocytes and the Renin Angiotensin System: Relevance in Disease Pathogenesis
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Endothelial Cells and the Cerebral Circulation
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Role of monocytes/macrophages in renin-angiotensin system-induced hypertension and end organ damage
Barhoumi, T., & Todryk, S. M. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1199934 · Cited by 17 · see citing works
Activation of the Protective Arm of the Renin Angiotensin System in Demyelinating Disease
Stone, R., Liu, S., Levy, A. M., Kashani, N., Louie, S. G., Rodgers, K. E., Kelland, E. E., & Lund, B. T. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09894-7 · Cited by 17 · see citing works
Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice
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Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
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Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT 1 receptor activation
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Glial cell activity in cardiovascular diseases and risk of acute myocardial infarction
Truter, N., Malan, L., & Essop, M. F. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00332.2022 · Cited by 13 · see citing works
Human Missense Mutations in Regulator of G Protein Signaling 2 Affect the Protein Function Through Multiple Mechanisms
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Gut microbiota and its metabolites: A potential approach for traditional Chinese medicine-derived non-starch polysaccharides to delay aging and prevent age-related diseases–A review
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Angiotensin-converting enzyme 2 activator, DIZE in the basolateral amygdala attenuates the tachycardic response to acute stress by modulating glutamatergic tone
Silva, C. C., Correa, A. M., Kushmerick, C., Sharma, N. M., Patel, K. P., Almeida, J. F., Moreira, F. A., Ferreira, A. J., & Fontes, M. A. P. (2020) · Neuropeptides · doi:10.1016/j.npep.2020.102076 · Cited by 12 · see citing works
Brain Renin–Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS‐CoV‐2
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Potentiation of NMDA Receptors by AT1 Angiotensin Receptor Activation in Layer V Pyramidal Neurons of the Rat Prefrontal Cortex
Hanuska, A., Ribiczey, P., Kató, E., Papp, Z. T., Varga, Z. V., Giricz, Z., Tóth, Z., Könczöl, K., Zsembery, Á., Zelles, T., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312644 · Cited by 11 · see citing works
Brain Angiotensin II Involvement in Chronic Mental Disorders
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Persistence of post-stress blood pressure elevation requires activation of astrocytes
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Analyzing the Complicated Connection Between Intestinal Microbiota and Cardiovascular Diseases
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Authors: de Kloet, A. D., Liu, M., Rodríguez, V., Krause, E. G., & Sumners, C.
Affiliations: Department of Physiology and Functional Genomics, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida; and
University of Florida Health (US)
Corresponding author: Sumners, Colin
ORCID: Liu, Meng
Krause, Eric G.
Sumners, Colin
Venue: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Publisher: American Physiological Society
Published: 2015-09
Volume: 309
Issue: 5
Pages: R444-R458
ISSN: 0363-6119 (ISSN-L)
1522-1490
DOI: 10.1152/ajpregu.00078.2015
PMC: PMC4591381
OpenAlex: W2198204313
Cited by: 64
References: 219
Citations by year: 2026: 1 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 9 · 2015: 1
FWCI: 1.38
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI) (HL-033610, HL-096830, HL-093186, F32-HL-116074, HL-076803, K99-HL-125805)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: renin-angiotensin system, angiotensin II, angiotensin II type 1 receptor, glial cells, microglia, neurons, blood pressure regulation, hypertension, cardiovascular regulation, neuroinflammation, antihypertensive peptides, central nervous system
MeSH terms: Angiotensin II, Animals, Blood Pressure, Cardiovascular System, Cell Communication, Central Nervous System, Humans, Hypertension, Neuroglia, Neurons, Renin-Angiotensin System, Receptor, Angiotensin, Type 1

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Role of neurons and glia in the CNS actions of the renin-angiotensin system in cardiovascular control

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