The renin-angiotensin system (RAS) is one of the oldest hormone systems in vertebrate phylogeny. RAS was initially related to regulation of blood pressure and sodium and water homeostasis. However, local or paracrine RAS were later identified in many tissues, including brain, and play a major role in their physiology and pathophysiology. In addition, a major component, ACE2, is the entry receptor for SARS-CoV-2. Overactivation of tissue RAS leads several oxidative stress and inflammatory processes involved in aging-related degenerative changes. In addition, a third level of RAS, the intracellular or intracrine RAS (iRAS), with still unclear functions, has been observed. The possible interaction between the intracellular and extracellular RAS, and particularly the possible deleterious or beneficial effects of the iRAS activation are controversial. The dopaminergic system is particularly interesting to investigate the RAS as important functional interactions between dopamine and RAS have been observed in the brain and several peripheral tissues. Our recent observations in mitochondria and nucleus of dopaminergic neurons may clarify the role of the iRAS. This may be important for the developing of new therapeutic strategies, since the effects on both extracellular and intracellular RAS must be taken into account, and perhaps better understanding of COVID-19 cell mechanisms.

肾素-血管紧张素系统（RAS）是脊椎动物系统发育中最古老的激素系统之一。RAS最初与血压，钠和水稳态的调节有关。然而，后来在包括脑在内的许多组织中发现了局部或旁分泌RAS，并且在其生理和病理生理中起着重要作用。另外，主要成分ACE2是SARS-CoV-2的进入受体。组织RAS过度活化会导致与衰老相关的退行性变化有关的多种氧化应激和炎症过程。另外，已经观察到第三水平的RAS，即细胞内或内分泌RAS（iRAS），其功能仍不清楚。细胞内和细胞外RAS之间可能的相互作用，尤其是iRAS激活的可能有害或有益作用是有争议的。多巴胺能系统对于研究RAS特别有趣，因为已经在大脑和一些外围组织中观察到多巴胺和RAS之间的重要功能相互作用。我们最近在多巴胺能神经元的线粒体和细胞核中的观察可能阐明了iRAS的作用。这对于开发新的治疗策略可能很重要，因为必须考虑对细胞外和细胞内RAS的影响，并且可能需要更好地了解COVID-19细胞机制。