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Aminopeptidase A inhibitors as centrally acting antihypertensive agents

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Abstract

Among the main bioactive peptides of the brain renin–angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for the type 1 and type 2 Ang receptors. Both peptides, injected intracerebroventricularly, cause similar increase in blood pressure (BP). Because AngII is converted in vivo to AngIII, the identity of the true effector is unknown. This review summarized recent insights into the predominant role of brain AngIII in the central control of BP underlining the fact that brain aminopeptidase A (APA), the enzyme forming central AngIII, could constitute a putative central therapeutic target for the treatment of hypertension. This led to the development of potent, systematically active APA inhibitors, such as RB150, as a prototype of a new class of centrally acting antihypertensive agents for the treatment of certain forms of hypertension.

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Acknowledgments

We would like to thank all of our collaborators for the work on the brain RAS especially Pr B. Roques, Pr M.-C. Fournie-Zaluski and Dr N. Inguimbert who designed and synthesized specific and selective APA and APN inhibitors. This study was financially supported by grants from the Agence Nationale de la Recherche (“EMERGENCE ET MATURATION” n° ANR-05-EMPB-015-02) and Quantum Genomics Corp. and by the Institut National de la Santé et de la Recherche Médicale.

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Bodineau, L., Frugière, A., Marc, Y. et al. Aminopeptidase A inhibitors as centrally acting antihypertensive agents. Heart Fail Rev 13, 311–319 (2008). https://doi.org/10.1007/s10741-007-9077-3

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