Late treatment with angiotensin-converting enzyme inhibitors plus endothelin receptor antagonists ameliorates rat tracheal allograft rejection

B. Antus, Janos Fillinger, Attila Sebe, Csaba Jeney, I. Horváth

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Inhibition of the renin-angiotensin and endothelin (ET) systems prevents the development of obliterative airway disease (OAD) in rat tracheal allografts. In this study, we assessed whether these therapeutic approaches are effective even when the same were started after signs of OAD were already manifest. Rat tracheas were heterotopically transplanted from Brown-Norway donors into Brown-Norway or Lewis recipients. Allograft recipients received bosentan, ramipril, bosentan plus ramipril or vehicle from day 10 to 24. Untreated allografts and isografts were harvested at day 10 or 24. In tracheal grafts, morphometric studies together with molecular analysis by real-time PCR were performed. Fibroproliferative process in untreated tracheal allografts but not in isografts started already at day 10. Neither bosentan nor ramipril treatment alone as monotherapy could modify the development of OAD when administered only between day 10 and day 24. By contrast, the combination treatment of bosentan and ramipril ameliorated airway obstruction by day 24, which was accompanied by reduced mRNA expression of intragraft transforming growth factor-β 1 and platelet-derived growth factor-A and -B chains. Only the combined blockade with angiotensin-converting enzyme inhibitors and ET receptor antagonists can reduce the progression of OAD in this model if the treatment is initiated late in the disease course.

Original languageEnglish
Pages (from-to)801-807
Number of pages7
JournalTransplant International
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 2008

Fingerprint

Ramipril
Angiotensin-Converting Enzyme Inhibitors
Allografts
Isografts
Norway
Proto-Oncogene Proteins c-sis
Endothelins
Transforming Growth Factors
Airway Obstruction
Renin-Angiotensin System
Trachea
Real-Time Polymerase Chain Reaction
Endothelin Receptor Antagonists
Transplants
Messenger RNA
bosentan

Keywords

  • Allograft
  • Bosentan
  • Ramipril
  • Rat
  • Rejection
  • Tracheal

ASJC Scopus subject areas

  • Transplantation

Cite this

Late treatment with angiotensin-converting enzyme inhibitors plus endothelin receptor antagonists ameliorates rat tracheal allograft rejection. / Antus, B.; Fillinger, Janos; Sebe, Attila; Jeney, Csaba; Horváth, I.

In: Transplant International, Vol. 21, No. 8, 08.2008, p. 801-807.

Research output: Contribution to journalArticle

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