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Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses

[ Vol. 20 , Issue. 1 ]

Author(s):

Michele Iovino, Tullio Messana, Giovanni De Pergola, Emanuela Iovino, Edoardo Guastamacchia, Brunella Licchelli, Aldo Vanacore, Vito A. Giagulli and Vincenzo Triggiani*   Pages 15 - 24 ( 10 )

Abstract:


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 neuroendocrine responses.

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.

Keywords:

Angiotensin, angiotensin receptors, immune system, oxidative stress, circumventricular organs, cardiovascular brain nuclei, autonomic and neuroendocrine outputs.

Affiliation:

Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Infantile Neuropsychiatry, IRCCS – Institute of Neurological Sciences, Bologna, Clinical Nutrition Unit, Medical Oncology, Department of Internal Medicine and Clinical Oncology, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari “Aldo Moro”, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari

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