Role of the Neuropeptide Angiotensin II in Stress and Related Disorders

Abstract

Angiotensin II (Ang II) was described as a peripheral hormone; its synthesis and metabolism were characterized and it is currently known as the renin-angiotensin system (RAS). All the components of the RAS, including the receptors, have been found in brain tissue, indicating a role as a hormone or neuromodulator in the central nervous system. Ang II exerts its principal known actions at the AT1 receptor. Its functions related to AT2 receptors are controversial and associated with AT1 opposite effects, although there is evidence showing cross-talk between both receptors. The metabolism of Ang II generates other active peptides, such as Angiotensin 1–7 and Angiotensin IV, which will not be discussed. Neurobiological research has explained many of the different neuroendocrine and behavioral responses to stressors. Stress is a complex phenomenon in response to physical, environmental, or psychological stimulus. Stress triggers important adaptive functions improving health and survival. Meanwhile, excessive stress can be deleterious, therefore, individuals unable to cope with stress are highly vulnerable to a variety of diseases. Stress is a major contributor of cardiovascular disorders and psychiatric illness such as anxiety and depression. Many studies have confirmed that stress also increases the vulnerability to drug abuse. The role of Ang II at the periphery and in the central nervous system is vast and complex. For this reason, in this chapter we will focus on the role of brain RAS in stress responses and related pathologies from many other important aspects of Ang II research.