Brain renin-angiotensin system in the pathophysiology of cardiovascular diseases

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Cardiovascular diseases (CVD) are among the main causes of death globally and in this context hypertension represents one of the key risk factors for developing a CVD. It is well established that the peripheral renin-angiotensin system (RAS) plays an important role in regulating blood pressure (BP). All components of the classic RAS can also be found in the brain but, in contrast to the peripheral RAS, how the endogenous RAS is involved in modulating cardiovascular effects in the brain is not fully understood yet. It is a complex system that may work differently in diverse areas of the brain and is linked to the peripheral system by the circumventricular organs (CVO), which do not have a blood brain barrier (BBB). In this review, we focus on the brain angiotensin peptides, their interactions with each other, and the consequences in the central nervous system (CNS) concerning cardiovascular control. Additionally, we present potential drug targets in the brain RAS for the treatment of hypertension.

Graphical abstract

The renin-angiotensin system (RAS) cascade. Symbol stimulation; inhibition;

Graphical abstract

Abbreviations: A779 Asp-Arg-Val-Tyr-Ile-His-D-Ala, ACE angiotensin-converting enzyme; ACE2 angiotensin-converting enzyme 2; APA aminopeptidase A; AngI Angiotensin I; APB aminopeptidase B; APN aminopeptidase N; DIZE diminazene aceturate; D-PRO d-Pro7-angiotensin(1–7); NEP neutral endopeptidase (neprilysin); PEP prolylendopeptidase;

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