ABSTRACT
The brain renin–angiotensin system (RAS) is critically involved in the cardiovascular regulation and energy homeostasis. The overwhelming evidence indicates that the central RAS closely cooperates with the systemic RAS by means of interactions with the autonomic nervous system and hormonal and humoral factors linking RAS with regulation of blood pressure, water–electrolyte equilibrium, and energy balance. Particularly significant roles in these interactions are played by aldosterone and vasopressin;however, other factors such as proinflammatory cytokines, growth factors, nitric oxide, prostaglandins, and ROS appear to be also essential players, especially during challenges (stress, hypoxia), and under pathological conditions (hypertension, heart failure, metabolic syndrome, atherosclerosis, COVID-19). Current pharmacotherapies of cardiovascular diseases are focused on the angiotensin-converting enzyme inhibitors and angiotensin type 1 receptor blockers and their effects on systemic RAS. A better understanding of neuroanatomical and neurochemical connections between central RAS and other regulatory systems should advance pharmacological interventions aimed at central RAS. © 2023 Elsevier Inc. All rights reserved.