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International Journal of Hypertension
Volume 2012, Article ID 124758, 12 pages
Review Article

Focus on Brain Angiotensin III and Aminopeptidase A in the Control of Hypertension

1Departments of Psychology and Veterinary and Comparative Anatomy, Pharmacology, and Physiology and Programs in Neuroscience and Biotechnology, Washington State University, P.O. Box 644820, Pullman, WA 99164-4820, USA
2Department of Medical Science of Proteases, Daiya Building Lady’s Clinic, Meieki 3-15-1, Nakamura, Nagoya 450-0002, Japan

Received 1 March 2012; Accepted 26 April 2012

Academic Editor: John R. Dietz

Copyright © 2012 John W. Wright et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The classic renin-angiotensin system (RAS) was initially described as a hormone system designed to mediate cardiovascular and body water regulation. The discovery of a brain RAS composed of the necessary functional components (angiotensinogen, peptidases, angiotensins, and specific receptor proteins) independent of the peripheral system significantly expanded the possible physiological and pharmacological functions of this system. This paper first describes the enzymatic pathways resulting in active angiotensin ligands and their interaction with AT1, AT2, and mas receptor subtypes. Recent evidence points to important contributions by brain angiotensin III (AngIII) and aminopeptidases A (APA) and N (APN) in sustaining hypertension. Next, we discuss current approaches to the treatment of hypertension followed by novel strategies that focus on limiting the binding of AngII and AngIII to the AT1 receptor subtype by influencing the activity of APA and APN. We conclude with thoughts concerning future treatment approaches to controlling hypertension and hypotension.