brain renin-angiotensin system

Definition

Target type: biologicalprocess

The process in which an angiotensin-mediated signaling system present in the brain regulates the force with which blood passes through the circulatory system. [PMID:2909574]

The brain renin-angiotensin system (RAS) is a complex and crucial system that plays a vital role in regulating various physiological processes within the central nervous system. Unlike the peripheral RAS, which primarily focuses on blood pressure regulation, the brain RAS exerts its influence on a wider range of functions, including thirst, salt appetite, blood pressure, stress response, and cognitive processes.

The brain RAS is characterized by the presence of all the components necessary for the synthesis and degradation of angiotensin II (Ang II), the primary effector of the system. These components include renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin-converting enzyme 2 (ACE2).

Renin, a proteolytic enzyme, is produced by neurons in specific regions of the brain, including the subfornical organ, the circumventricular organs, and the hypothalamus. Its release is triggered by various stimuli, such as dehydration, sodium depletion, and stress. Renin cleaves angiotensinogen, a precursor protein produced in the liver, to generate angiotensin I (Ang I).

Ang I is then converted to the active peptide Ang II by ACE, an enzyme primarily localized in the endothelium of blood vessels. ACE is also expressed in the brain, primarily in the circumventricular organs and the hypothalamus. Ang II acts as the main effector of the brain RAS, binding to specific receptors located on neurons and glial cells.

The brain RAS also involves the action of ACE2, an enzyme that competes with ACE for Ang I as a substrate. ACE2 converts Ang I to Ang 1-7, a peptide with opposing actions to Ang II. Ang 1-7 binds to the Mas receptor, activating signaling pathways that counteract the effects of Ang II.

The brain RAS exerts its effects through multiple mechanisms, including:

- Direct action on neurons: Ang II binds to Ang II receptors (AT1 and AT2) on neurons, triggering various signaling pathways that regulate neuronal activity and neurotransmitter release.
- Modulation of neurotransmitter release: Ang II influences the release of various neurotransmitters, including dopamine, norepinephrine, serotonin, and glutamate, playing a role in regulating mood, cognition, and behavior.
- Regulation of blood-brain barrier permeability: Ang II can alter the permeability of the blood-brain barrier, influencing the transport of nutrients, hormones, and drugs across the barrier.
- Control of thirst and salt appetite: Ang II stimulates thirst and salt appetite, helping to maintain fluid and electrolyte balance.
- Integration with other brain systems: The brain RAS interacts with other brain systems, including the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the immune system, contributing to the regulation of stress response, blood pressure, and inflammation.

The brain RAS is implicated in various physiological and pathological conditions, including:

- Hypertension: Ang II plays a crucial role in the development and maintenance of hypertension, both centrally and peripherally.
- Cardiovascular disease: The brain RAS contributes to cardiovascular disease by influencing heart rate, blood pressure, and vascular tone.
- Stroke: Ang II has been shown to exacerbate stroke damage by promoting inflammation and neuronal cell death.
- Alzheimer's disease: The brain RAS is implicated in the pathogenesis of Alzheimer's disease, contributing to cognitive decline and neuronal dysfunction.
- Depression: The brain RAS is involved in the regulation of mood and stress response, and alterations in its activity have been linked to depression.

The brain RAS is a complex and fascinating system that continues to be actively researched. Understanding its intricate mechanisms and roles in various physiological and pathological processes will provide valuable insights into the development of novel therapeutic strategies for a wide range of diseases.'
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Proteins (1)

Compounds (29)