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Angiotensin generation in the brain: a re-evaluation
Estrellita Uijl1, Liwei Ren1, A H Jan Danser2
1Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Clinical Science (London, England : 1979)
|May 2, 2018
Summary
Independent angiotensin generation in the brain is unlikely. Angiotensin in the brain likely originates from the blood, especially when the blood-brain barrier is compromised.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Molecular Biology
Background:
- The existence and function of a brain renin-angiotensin system (RAS) are debated.
- Angiotensin generation within the brain requires local renin and angiotensinogen synthesis.
- The blood-brain barrier poses a significant obstacle to central angiotensin production.
Purpose of the Study:
- To critically evaluate the evidence for independent angiotensin generation in the brain.
- To investigate the roles of brain renin, angiotensinogen, and the (pro)renin receptor in central RAS.
- To propose a unifying concept for angiotensin's origin in the brain.
Main Methods:
- Review of existing literature on brain renin-angiotensin system components.
- Analysis of data from intracellular renin knockout animal models.
- Examination of studies on prorenin expression and (pro)renin receptor function in the brain.
- Assessment of angiotensinogen mRNA and protein levels in brain tissue.
- Evaluation of brain angiotensin I and II levels in relation to blood and receptor binding.
Main Results:
- Evidence argues against a significant role for intracellular renin in brain angiotensin generation.
- Renin levels in brain tissue likely represent trapped blood renin.
- No convincing evidence for brain prorenin expression or its selective upregulation in neurogenic hypertension.
- The (pro)renin receptor appears to have RAS-independent functions.
- Brain angiotensinogen protein levels are low and potentially overestimated.
- Brain angiotensin levels are very low, reflecting blood-derived angiotensin.
Conclusions:
- Independent angiotensin generation within the brain is improbable.
- Angiotensin in the brain primarily originates from the bloodstream.
- Increased brain angiotensin levels may occur with blood-brain barrier disruption, such as in hypertension.
- Interventions targeting intracellular renin or the (pro)renin receptor may exert effects independent of the classical RAS.
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