ERNEST H. STARLING DISTINGUISHED LECTURESHIP OF THE APS WATER AND ELECTROLYTE HOMEOSTASIS SECTION, 2011 Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system

Sigmund CD. Divergent mechanism regulating fluid intake and metabolism by the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol 302: R313– R320, 2012. First published November 2, 2011; doi:10.1152/ajpregu.00575.2011.— The purpose of this review is two-fold. First, I will highlight recent advances in our understanding of the mechanisms regulating angiotensin II (ANG II) synthesis in the brain, focusing on evidence that renin is expressed in the brain and is expressed in two forms: a secreted form, which may catalyze extracellular ANG I generation from glial or neuronal angiotensinogen (AGT), and an intracellular form, which may generate intracellular ANG in neurons that may act as a neurotransmitter. Second, I will discuss recent studies that advance the concept that the reninangiotensin system (RAS) in the brain not only is a potent regulator of blood pressure and fluid intake but may also regulate metabolism. The efferent pathways regulating the blood pressure/dipsogenic effects and the metabolic effects of elevated central RAS activity appear different, with the former being dependent upon the hypothalamic-pituitary-adrenal axis, and the latter being dependent upon an interaction between the brain and the systemic (or adipose) RAS.