Document Detail

Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells.
MedLine Citation:
PMID:  16528246     Owner:  NLM     Status:  MEDLINE    
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% vs vehicle, P<0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis.
W S Almeida; T T Maciel; G S Di Marco; D E Casarini; A H Campos; N Schor
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international     Volume:  69     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-10     Completed Date:  2006-06-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  974-80     Citation Subset:  IM    
Departament of Medicine, Nephrology Division, Universidade Federal de São Paulo, São Paulo, Brazil.
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MeSH Terms
Angiotensin I / analysis,  metabolism
Angiotensin II / analysis,  metabolism*
Angiotensinogen / pharmacology
Blotting, Western
Cell Line
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Endotoxemia / physiopathology
Escherichia coli / chemistry*
Lipopolysaccharides / analysis*,  pharmacology*
Mesangial Cells / chemistry,  drug effects*,  physiology
Peptidyl-Dipeptidase A / analysis,  physiology
Renin / analysis,  antagonists & inhibitors,  drug effects*,  physiology
Renin-Angiotensin System / drug effects,  physiology
Time Factors
Reg. No./Substance:
0/Lipopolysaccharides; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 9041-90-1/Angiotensin I; EC A; EC

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