Multiple Aspects of Inappropriate Action of Renin-Angiotensin, Vasopressin, and Oxytocin Systems in Neuropsychiatric and Neurodegenerative Diseases

Abstract

The cardiovascular system and the central nervous system (CNS) closely cooperate in the regulation of primary vital functions. The autonomic nervous system and several compounds known as cardiovascular factors, especially those targeting the renin-angiotensin system (RAS), the vasopressin system (VPS), and the oxytocin system (OTS), are also efficient modulators of several other processes in the CNS. The components of the RAS, VPS, and OTS, regulating pain, emotions, learning, memory, and other cognitive processes, are present in the neurons, glial cells, and blood vessels of the CNS. Increasing evidence shows that the combined function of the RAS, VPS, and OTS is altered in neuropsychiatric/neurodegenerative diseases, and in particular in patients with depression, Alzheimer's disease, Parkinson's disease, autism, and schizophrenia. The altered function of the RAS may also contribute to CNS disorders in COVID-19. In this review, we present evidence that there are multiple causes for altered combined function of the RAS, VPS, and OTS in psychiatric and neurodegenerative disorders, such as genetic predispositions and the engagement of the RAS, VAS, and OTS in the processes underlying emotions, memory, and cognition. The neuroactive pharmaceuticals interfering with the synthesis or the action of angiotensins, vasopressin, and oxytocin can improve or worsen the effectiveness of treatment for neuropsychiatric/neurodegenerative diseases. Better knowledge of the multiple actions of the RAS, VPS, and OTS may facilitate programming the most efficient treatment for patients suffering from the comorbidity of neuropsychiatric/neurodegenerative and cardiovascular diseases.

Keywords: COVID-19; analogues of angiotensins; cardiovascular disorders; cognition; emotions; neuropsychiatric/neurodegenerative disorders; oxytocin; stress; vasopressin.

Figure 1

The brain structures involved in the regulation of the cardiovascular, cognitive, emotional, and behavioral functions through actions exerted by the renin–angiotensin system (RAS), and the vasopressin (AVP) and oxytocin (OT) systems. Abbreviations: Ang II—angiotensin II; Ang-(1-7)—angiotensin-(1-7); AP—area postrema; CVLM—caudal ventrolateral medulla, CVOs—circumventricular organs; IML—intermediolateral column; NTS—nucleus of the solitary tract; OVLT—organum vasculosum laminae terminalis; PAG—periaqueductal gray; PFC—prefrontal cortex; PVN—paraventricular nucleus; RVLM—rostral ventrolateral medulla; SFO—subfornical organ; 3rdV—third ventricle.

Figure 2

The main components of the renin–angiotensin system (RAS) engaged in the regulation of cardiovascular, cognitive, emotional, and behavioral functions. Abbreviations: ACE—angiotensin converting enzyme; ACEI—inhibitor of ACE; Ang—angiotensin; APA, APB, and APN—aminopeptidases A, B, and N; AT1R, AT2R—angiotensin receptors; AVP—arginine vasopressin; CNS—central nervous system; IRAP—insulin-regulated aminopeptidase; MasR—Mas receptor of Ang-(1-7); NEP—neutral endopeptidase; OT—oxytocin; OTR—oxytocin receptor; V1aR, V1bR, V2R—vasopressin receptors. See also refrences [16,17].