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.
Highlights
The cardiovascular system and the central nervous system (CNS) closely cooperate in the regulation of primary vital functions
Measurements of copeptin, which is a surrogate marker of addition to elevating plasma vasopressin (AVP), indicate that blood copeptin levels are elevated in patients who are insensitive to antidepressant treatment, and it appears that copeptin may be a useful biomarker for the early selection of non-responders to specific antidepressant treatments [136]
A survey of the literature shows that the renin–angiotensin system (RAS), vasopressin system (VPS), and oxytocin system (OTS), the classical endocrine systems regulating blood pressure and the water-electrolyte balance, are potent regulators of other CNS processes through their actions on cerebral blood flow, the metabolism, and intercellular and intracellular signal transmission
Summary
ACE is expressed mainly by the endothelial cells of the pulmonary vessels, but it is present in the brain, heart, and other organs. Stimulation of AT2R is associated with the activation of phosphotyrosine phosphatases, especially serine/threonine phosphatase 2A, protein kinase phosphatase, and SHP-1 tyrosine phosphatase. It causes the inactivation of mitogen activated protein kinases (MAPK), p42 and p44 MAPK [35]. It has been shown that the Ang IV/AT4R pathway in the brain interacts with the hepatocyte growth factor/c-Met receptor system [39]. Activates the Mas receptors (MasRs) and the ACE2/Ang-(1-7)/Mas axis [40,41,42]
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