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Is the renin–angiotensin system actually hypertensive?

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Abstract

The historical view of the renin–angiotensin system (RAS) is that of an endocrine hypertensive system that is controlled by renin and mediated via the action of angiotensin II on its type 1 receptor. Numerous new angiotensins (Ang) and receptors have been described, the majority being hypotensive and natriuretic, namely Ang-(1-7) and its receptor rMas. Renin and its precursor (pro-renin) can bind their common receptor. In addition to the production of Ang II, this receptor triggers intracellular effects. Given the control of renin production by intracellular calcium, calcium homeostasis is of particular importance. Ang-(1-12), which is not controlled by renin, is converted to several different angiotensin peptides and is a new pathway of the RAS. Local RAS enzymes produce or transform the different hyper- or hypotensive angiotensin within vessels and organs, but also in blood through circulating forms of the enzymes. In the kidney, a powerful local vascular RAS allows for the independence of renal vascularization from systemic control. Moreover, the kidney also contains an independent urinary RAS, which counterbalances the systemic RAS and coordinates proximal and distal sodium reabsorption. The systemic and local effects of renal RAS cannot be analyzed without taking into account the antagonistic effect of renalase. Our concept of RAS needs to evolve to take into account its dual potentiality (hyper- or hypotensive).

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Acknowledgments

The authors would like to thank Professor Vincent Esnault for his fruitful comments.

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Authors and Affiliations

  1. Unité de néphrologie pédiatrique, Hôpital Archet 2, Hôpitaux pédiatriques universitaires de Nice, 151 route de Saint Antoine Ginestière, 06202, Nice cedex 3, France

    Etienne Bérard & Olivier Niel

  2. Clinique Universitaire de Pédiatrie, Hôpital Couple-Enfant, Centre Hospitalier Universitaire (CHU) de Grenoble., Avenue des Maquis du Grésivaudan, 38700, La Tronche, France

    Amandine Rubio

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  1. Etienne Bérard
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  2. Olivier Niel
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  3. Amandine Rubio
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Correspondence to Etienne Bérard.

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Bérard, E., Niel, O. & Rubio, A. Is the renin–angiotensin system actually hypertensive?. Pediatr Nephrol 29, 951–960 (2014). https://doi.org/10.1007/s00467-013-2481-0

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