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Status: Bibliographieeintrag

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Verfasst von:Braun, Claude [VerfasserIn]   i
 Conzelmann, Tobias [VerfasserIn]   i
 Vetter, Stephan [VerfasserIn]   i
 Schaub, Meike [VerfasserIn]   i
 Back, Walter [VerfasserIn]   i
 Yard, Benito A. [VerfasserIn]   i
 Kirchengast, Michael [VerfasserIn]   i
 Tullius, Stefan Günther [VerfasserIn]   i
 Schnülle, Peter [VerfasserIn]   i
 Woude, Fokko J. van der [VerfasserIn]   i
 Rohmeiss, Peter [VerfasserIn]   i
Titel:Prevention of chronic renal allograft rejection in rats with an oral endothelin A receptor antagonist
Verf.angabe:C. Braun, T. Conzelmann, S. Vetter, M. Schaub, W.E. Back, B. Yard, M. Kirchengast, S.G. Tullius, P. Schnülle, F.J. van der Woude, P. Rohmeiss
Jahr:1999
Umfang:8 S.
Fussnoten:Gesehen am 22.09.2022
Titel Quelle:Enthalten in: Transplantation
Ort Quelle:Hagerstown, Md. : Lippincott Williams & Wilkins, 1963
Jahr Quelle:1999
Band/Heft Quelle:68(1999), 6, Seite 739-746
ISSN Quelle:1534-6080
Abstract:BACKGROUND: Chronic rejection is the most common cause of graft loss in renal transplantation. The pathomechanisms underlying chronic rejection are poorly understood, and no treatment has yet successfully been established. We hypothesized that, in analogy to models of reduced renal mass, the administration of a selective endothelin (ET) A receptor antagonist could improve the course of chronic rejection in renal allografts. METHODS: Experiments were performed in the Fisher-to-Lewis rat model of chronic rejection. Lewis-->Lewis isografts served as controls. Animals were treated with either the oral selective ET-A receptor antagonist LU135252 (50 mg/kg/day) or vehicle. Animal survival, blood pressure, creatinine clearance, proteinuria, and urinary ET excretion were investigated for 24 weeks. Kidneys were removed for light microscopical evaluation, determination of ET mRNA expression and tissue protein concentration, and immunohistochemical assessment of cell surface markers. RESULTS: Rats with chronic rejection showed an increase in renal ET mRNA synthesis and ET protein content. Treatment with LU135252 resulted in a significant improvement in survival after 24 weeks (0.92 vs. 0.38, P<0.01 by log-rank test). Creatinine clearance was higher in animals treated with the selective ET-A receptor antagonist (P<0.05). LU135252 had no influence on blood pressure and proteinuria. Selective ET-A blockade was associated with significantly less morphological changes and a significant reduction of expression of cell surface markers for macrophages (ED1), T cells (R73), and MHC II (F17-23-2). CONCLUSION: The renal ET-A system plays an important role in the pathomechanisms underlying chronic renal allograft rejection, because the treatment with a selective ET-A receptor antagonist dramatically improves the course of chronic renal failure after allograft transplantation. These results offer a novel therapeutical option for treatment of chronic renal allograft rejection, for which so far no therapy is known.
DOI:doi:10.1097/00007890-199909270-00005
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1097/00007890-199909270-00005
 DOI: https://doi.org/10.1097/00007890-199909270-00005
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Administration, Oral
 Animals
 Endothelin Receptor Antagonists
 Endothelin-1
 Endothelins
 Graft Rejection
 Graft Survival
 Kidney Diseases
 Kidney Glomerulus
 Kidney Transplantation
 Male
 Phenylpropionates
 Pyrimidines
 Rats
 Rats, Inbred F344
 Rats, Inbred Lew
 Receptor, Endothelin A
 Receptors, Endothelin
 RNA, Messenger
K10plus-PPN:1817293745
Verknüpfungen:→ Zeitschrift

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