Transgenic Models in Neuroendocrinology Neuroendocrinology 2003;78:253–259 DOI: 10.1159/000074446 Brain Renin-Angiotensin System Lessons from Functional Genomics Ovidiu Baltatu Michael Bader Max-Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany Received: June 13, 2003 Accepted after revision: September 8, 2003 Ovidiu Baltatu Max-Delbrück Center for Molecular Medicine (MDC) Robert-Rössle-Strasse 10 DE–13125 Berlin-Buch (Germany) Tel. +49 30 9406 2397, Fax +49 30 9406 2710, E-Mail baltatu@mdc-berlin.de ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2003 S. Karger AG, Basel 0028–3835/03/0785–0253$19.50/0 Accessible online at: www.karger.com/nen Key Words Angiotensins W Brain renin-angiotensin system W Molecular neuroendocrinology W Electrolyte homeostasis W Blood pressure W Hypertension Abstract The existence of a brain renin-angiotensin system (RAS) was postulated 30 years ago. Since then our knowledge on the biology of the brain RAS has advanced consider- ably. The brain RAS has been found to be involved in the modulation of cardiovascular and fluid-electrolyte ho- meostasis, generally complementing the classical roles of the endocrine RAS. The RAS has additionally been implicated in other brain-specific functions, such as memory, cognition and stress. During the last years, the development of transgenic technologies allowed to get further insight into the functionality and relevance of the brain RAS. This paper is attempting to summarize our recent experience from transgenic animals. Copyright © 2003 S. Karger AG, Basel The brain renin-angiotensin systems (RAS) is distinc- tive from the other local tissue RASs since it is physically separated from the endocrine one by the presence of the blood-brain barrier impeding the penetration of angioten- sin from blood into the brain [1–3]. Circulating Ang II may, however, transmit effects inside the brain through areas lacking the blood-brain barrier [4]. Numerous neu- rophysiological studies have ascertained the implication of the brain RAS in the modulation of cardiovascular and fluid-electrolyte homeostasis [4], by modulating the activ- ity of the autonomic nervous system [5–7], hypothalamic- pituitary axis and vasopressin release [8], baroreflex sensi- tivity [9] and stimulating thirst [10, 11]. In addition, brain-specific functions have been attributed to the RAS, such as influencing memory, cognition and stress [12]. The development of molecular biology methodologies led to the cloning of the RAS components, allowing iden- tification of their synthesis in distinct brain areas. Angio- tensinogen (AOGEN), the only known source of angioten- sins, is also produced in the brain [13–15]. It is widely distributed throughout various brain regions, high levels are found in hypothalamus and brain stem, which are brain areas important for the central control of homeosta- sis. Astroglia represents the main cell type synthesizing AOGEN [16] (reviewed in [4]). Renin and angiotensin- converting enzyme (ACE) – as classical enzymes responsi- ble for the conversion of AOGEN into active products – have been detected in the brain. Although renin activity and immunoreactivity are high in hypothalamus, pitu- itary and pineal glands (reviewed in [4]), renin mRNA levels are low or under the detection limit [17]. ACE activ- ity and its mRNA are high in areas lacking the blood- brain barrier such as diencephalon, pituitary and pineal