The existence of a so-called brain renin-angiotensin system (RAS) is controversial. Given the presence of the blood–brain barrier, angiotensin generation in the brain, if occurring, should depend on local synthesis of renin and angiotensinogen. Yet, although initially brain-selective expression of intracellular renin was reported, data in intracellular renin knockout animals argue against a role for this renin in angiotensin generation. Moreover, renin levels in brain tissue at most represented renin in trapped blood. Additionally, in neurogenic hypertension brain prorenin up-regulation has been claimed, which would generate angiotensin following its binding to the (pro)renin receptor. However, recent studies reported no evidence for prorenin expression in the brain, nor for its selective up-regulation in neurogenic hypertension, and the (pro)renin receptor rather displays RAS-unrelated functions. Finally, although angiotensinogen mRNA is detectable in the brain, brain angiotensinogen protein levels are low, and even these low levels might be an overestimation due to assay artefacts. Taken together, independent angiotensin generation in the brain is unlikely. Indeed, brain angiotensin levels are extremely low, with angiotensin (Ang) I levels corresponding to the small amounts of Ang I in trapped blood plasma, and Ang II levels at most representing Ang II bound to (vascular) brain Ang II type 1 receptors. This review concludes with a unifying concept proposing the blood origin of angiotensin in the brain, possibly resulting in increased levels following blood–brain barrier disruption (e.g. due to hypertension), and suggesting that interfering with either intracellular renin or the (pro)renin receptor has consequences in an RAS-independent manner.
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A representation of the intestinal microflora. In Clinical Science volume 132 (issue 7), Rajani and Jia review recent research on the effect of bacterial metabolites on host metabolism (microbiota-host co-metabolism) associated with conditions such as obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (pages 791-811). Then, in issue 8, Lezutekong et al. (pages 901-904) provide a commentary on a recent research by Kim et al. in Clinical Science that demonstrates a crucial link between gut microbiota and bacterial metabolites such as butyrate, gut leakiness, and hypertension. These and other articles from the journal are featured in a themed collection on the topic of the microbiome and chronic disease.
Review Article|
April 30 2018
Angiotensin generation in the brain: a re-evaluation
Estrellita Uijl;
Estrellita Uijl
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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Liwei Ren;
Liwei Ren
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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A.H. Jan Danser
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
Correspondence: A.H. Jan Danser ([email protected])
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Publisher: Portland Press Ltd
Received:
March 18 2018
Revision Received:
April 09 2018
Accepted:
April 09 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (8): 839–850.
Article history
Received:
March 18 2018
Revision Received:
April 09 2018
Accepted:
April 09 2018
Citation
Estrellita Uijl, Liwei Ren, A.H. Jan Danser; Angiotensin generation in the brain: a re-evaluation. Clin Sci (Lond) 30 April 2018; 132 (8): 839–850. doi: https://doi.org/10.1042/CS20180236
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