PDI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Perit Dial Int 27(2): 167-172 2007
© 2007 International Society for Peritoneal Dialysis
This Article
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sauter, M.
Right arrow Articles by Sitter, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sauter, M.
Right arrow Articles by Sitter, T.

Basic Research

ACE INHIBITOR AND AT1-RECEPTOR BLOCKER ATTENUATE THE PRODUCTION OF VEGF IN MESOTHELIAL CELLS

Matthias Sauter1, Clemens D. Cohen1, Markus Wörnle1, Thomas Mussack2, Roland Ladurner2 and Thomas Sitter1

1 Department of Nephrology, Medizinische Poliklinik - Innenstadt; 2 Department of Surgery - Innenstadt, Klinikum der Universität München, München, Germany

Correspondence to: M. Sauter, Medizinische Poliklinik-Innenstadt, Klinikum der Universitaet Muenchen, Petten-koferstr. 8a, 80336 München, Germany.
Matthias.Sauter{at}med.uni-muenchen.de

{diamondsuit} Objective: Human mesothelial cells (HMC) are a major source of intraperitoneal vascular endothelial growth factor (VEGF) and by that are presumably involved in complications of long-term peritoneal dialysis (PD), such as ultrafiltration failure. This prompted us to look for agents that reduce basic mesothelial VEGF production and abrogate VEGF-overproduction induced by proinflammatory cytokines such as tumor necrosis factor alpha (TNF-{alpha}) and interleukin-1{alpha} (IL-1{alpha}). Angiotensin-converting enzyme (ACE) inhibition was found to preserve peritoneal function and ameliorate morphologic changes in a rat PD model. The present in vitro study was designed to investigate the effect of the ACE inhibitors captopril and enalapril, and the angiotensin II type 1-receptor (AT1) antagonist losartan on mesothelial VEGF synthesis.

{diamondsuit} Methods: HMC were isolated from omental tissue and taken into culture. VEGF antigen concentrations were measured in the cell supernatant by ELISA. VEGF mRNA levels were determined by real-time polymerase chain reaction.

{diamondsuit} Results: Incubation of HMC with captopril (100-1000 µmol/L) resulted in a concentration-dependent attenuation of VEGF synthesis. Incubation with captopril (500-1000 µmol/L), enalapril (100-1000 µmol/L), and losartan (1-100 µmol/L) significantly decreased inflammatory mediator (TNF-{alpha}, IL-1{alpha})-induced mesothelial VEGF overproduction.

{diamondsuit} Conclusion: The results indicate that ACE inhibitors and AT1-receptor blockers are capable of effectively attenuating the overproduction of VEGF due to proinflammatory cytokine stimuli. These data suggest that locally produced angiotensin II in the peritoneal cavity may be a potential therapeutic target in ultrafiltration failure during longterm PD.

KEY WORDS: KEY WORDS:; Mesothelial cells; vascular endothelial growth factor; ACE inhibitor; AT1-receptor blocker.

Received 20 October 2006; accepted 12 January 2007.




This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
L. S. Aroeira, A. Aguilera, J. A. Sanchez-Tomero, M. A. Bajo, G. del Peso, J. A. Jimenez-Heffernan, R. Selgas, and M. Lopez-Cabrera
Epithelial to Mesenchymal Transition and Peritoneal Membrane Failure in Peritoneal Dialysis Patients: Pathologic Significance and Potential Therapeutic Interventions
J. Am. Soc. Nephrol., July 1, 2007; 18(7): 2004 - 2013.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Multimed Inc. logo
Copyright © 2007 by Multimed Inc.