Receptor Mas protects mice against hypothermia and mortality induced by endotoxemia

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Item Type:	Article
Title:	Receptor Mas protects mice against hypothermia and mortality induced by endotoxemia
Creators Name:	Souza, L.L., Duchene, J., Todiras, M., Azevedo, L.C.P., Costa-Neto, C.M., Alenina, N., Santos, R.A. and Bader, M.
Abstract:	The renin angiotensin system (RAS) is involved in maintaining cardiovascular function by regulating blood pressure and electrolyte homeostasis. More recently, alternative pathways within the RAS have been described, such as the ACE2/Ang-(1-7)/Mas axis with opposite effects to the ones of the ACE/AngII/AT1 axis. Correspondingly, our previous work reported that Ang-(1-7) via its receptor Mas inhibits the mRNA expression of the pro-inflammatory cytokines, IL-6 and TNF-{alpha} increased by LPS in mouse peritoneal macrophages. These data led us to investigate the functional role of the Ang-(1-7)/Mas axis in an in vivo LPS model. In this work, we present evidence that Ang-(1-7) via Mas significantly reduced the LPS-increased production of circulating cytokines, such as IL-6, IL-12, and CXCL-1. This inhibitory effect was mediated by Mas since it was not detectable in Mas mice. Accordingly, IL-6, CXCL-1 and CXCL-2 levels were higher after LPS treatment in the absence of Mas. Mas mice were less resistant to LPS-induced endotoxemia, their survival rate being 50% compared to 95% in wild type mice. Telemetric analyses showed that Mas mice presented more pronounced LPS-induced hypothermia with a 3°C lower body temperature compared to wild type mice. Altogether, our findings suggest that Ang-(1-7) and Mas inhibit LPS induced cytokine production and hypothermia and thereby protect mice from the fatal consequences of endotoxemia.
Keywords:	Angiotensin 1-7, Lipopolysaccharide, Cytokines, Macrophages, Body Temperature, Inflammation, Animals, Mice
Source:	Shock
ISSN:	1073-2322
Publisher:	Lippincott Williams & Wilkins
Volume:	41
Number:	4
Page Range:	331-336
Date:	April 2014
Official Publication:	https://doi.org/10.1097/SHK.0000000000000115
PubMed:	View item in PubMed

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