Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells

Kidney International
W S AlmeidaN Schor

Abstract

Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. The present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 microg/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. In addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P<0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P<0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% v...Continue Reading

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Jul 23, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Magali AraujoKenneth L Becker
Sep 25, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Chung-Hsi HsingChing-Hua Yeh
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Dec 17, 2009·Expert Opinion on Therapeutic Targets·Diamantino Ribeiro SalgadoJean-Louis Vincent
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Jan 18, 2019·Critical Care Medicine·Patrick J GleesonJacques Creteur
Jun 3, 2016·American Journal of Physiology. Renal Physiology·Rodolfo Mattar RosaDulce Elena Casarini
Jun 19, 2014·Experimental and Therapeutic Medicine·Wei ZhangYuguo Chen

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