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Jacques Benoit lecture: the neuroendocrine view of the angiotensin and apelin systems.

Catherine Llorens-Cortes 1, * Claude Kordon 2
* Corresponding author
1 Neuropeptides centraux et régulations hydrique et cardiovasculaire
UPMC - Université Pierre et Marie Curie - Paris 6, CIRB - Centre interdisciplinaire de recherche en biologie, INSERM - Institut National de la Santé et de la Recherche Médicale : U691
Abstract : The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase arginine vasopressin (AVP) release and blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. We review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme generating brain Ang III, may therefore be an interesting candidate target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension. We also searched for a putative angiotensin receptor subtype specific for Ang III and isolated a seven transmembrane-domain G protein-coupled receptor corresponding to the receptor for apelin, a newly-discovered peptide isolated from bovine stomach. Apelin and its receptor are expressed in magnocellular vasopressinergic neurones in the hypothalamus. The central injection of apelin in lactating rats decreases the phasic electrical activity of vasopressinergic neurones and the systemic secretion of AVP, inducing water diuresis. Apelin is therefore a natural inhibitor of the antidiuretic effect of AVP. In addition, systemic administration of apelin decreases BP, improves cardiac contractility and reduces cardiac loading. The development of nonpeptide agonists of the apelin receptor may provide new therapeutic tools for treating water retention, hyponatraemia and cardiovascular diseases. Angiotensins and apelin thus exert opposing but complementary effects, and are thereby determinant for the maintenance of body fluid homeostasis and cardiovascular functions.
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https://www.hal.inserm.fr/inserm-00422690
Contributor : Catherine Llorens Cortes <>
Submitted on : Thursday, October 8, 2009 - 12:03:26 PM
Last modification on : Wednesday, September 23, 2020 - 4:33:16 AM

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Catherine Llorens-Cortes, Claude Kordon. Jacques Benoit lecture: the neuroendocrine view of the angiotensin and apelin systems.. Journal of Neuroendocrinology, Wiley, 2008, 20 (3), pp.279-89. ⟨10.1111/j.1365-2826.2007.01642.x⟩. ⟨inserm-00422690⟩

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