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Aminopeptidase Inhibitors as Anti-Hypertensive Drugs

  • Chapter
Aminopeptidases in Biology and Disease

Part of the book series: Proteases in Biology and Disease ((PBAD,volume 2))

Abstract

This review summarizes what is currently known about the molecular and biochemical properties of aminopeptidase A (EC 3.4.11.7, APA), and its physiological role, together with aminopeptidase N (EC 3.4.11.2, APN) in the in vivo metabolism of brain angiotensin (Ang) II and AngIII. Exploration of the APA active site, the construction of a three-dimensional model of the APA ectodomain and the development of specific and selective APA and APN inhibitors have allowed to demonstrate that 1) Anglll, generated by APA, is a major effector peptide of the brain renin-angiotensin system, exerting tonic central control over blood pressure (BP), at least in conscious hypertensive animals and 2) the inhibition of central, but not peripheral, APA by specific and selective inhibitors leads to a decrease in BP in hypertensive animals. Central APA may therefore be an interesting candidate target for the treatment of hypertension, which justifies the development of potent and selective APA inhibitors that cross the blood brain barrier as putative central antihypertensive agents.

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Authors and Affiliations

  1. INSERM U36 — College de France, 75005, Paris, France

    Xavier Iturrioz, Annabelle Reaux, Le Goazigo & Catherine Llorens-Cortes

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  2. Annabelle Reaux
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  1. University of Leeds, Leeds, UK

    Nigel M. Hooper

  2. Otto-von-Guericke University, Magdeburg, Germany

    Uwe Lendeckel

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Iturrioz, X., Reaux, A., Goazigo, L., Llorens-Cortes, C. (2004). Aminopeptidase Inhibitors as Anti-Hypertensive Drugs. In: Hooper, N.M., Lendeckel, U. (eds) Aminopeptidases in Biology and Disease. Proteases in Biology and Disease, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8869-0_11

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  • DOI: https://doi.org/10.1007/978-1-4419-8869-0_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4698-2

  • Online ISBN: 978-1-4419-8869-0

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