Objective: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the
regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We
perform a review of the literature, aiming at providing the current concepts regarding the angiotensin
interaction with the immune system in the brain and the related implications for cardiovascular and
Methods: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally,
references of original articles and reviews were examined.
Results: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release,
sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune
system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal
gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into
the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes
permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular
functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema,
paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral
medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided
with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration
of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition
of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the
development of hypertension.
Conclusion: Besides the well-known mechanisms by which RAAS activation can lead to the development
of hypertension, the interactions between ANG II and the immune system at the brain level can
play a significant role.