title: Expression of NO Synthase Under Medication with Cyclosporine A, Mycophenolate Mofetil, and Tacrolimus during Development of Transplant Vasculopathy on Rat Cardiac Allograft.
abstract: OBJECTIVE
  The transplant vasculopathy as a sign of chronic graft rejection affects both the epicardial and the intramyocardial arteries of the graft. This is at least partially mediated by NO synthases. The aim of this study was to assess possible protective effects of cyclosporine A (CsA), tacrolimus (FK506), and mycophenolate mofetil (MMF) on the expression of NO synthases in an experimental transplant rat model.
  
  
  OBJECTIVE
  Heart transplantation was performed in 322 rats. These were randomly assigned to four equal groups (control, CsA, FK506, MMF). Recipients were monitored up to 60 days after transplantation, while transplanted hearts were recovered at certain time points for analysis. Expression and staining intensity for endothelial nitric oxide synthases (e-nos) and inducible nitric oxide synthases (i-nos) were analyzed in epicardial and intramyocardial vessels in each group.
  
  
  RESULTS
  All employed drugs led to a significant reduction of expression or staining intensity of i-nos and e-nos. MMF was most effective in reduction in expression of both NO synthases.
  
  
  CONCLUSIONS
  These results imply that all described drugs prevent endothelial impairment induced by toxicity of NO and thereby prevent transplant vasculopathy. MMF seems to be the most effective drug.
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, Ludenscheid, Germany.|Department of Cardiology, Witten / Herdecke University, Witten, Germany.
authors.forename: Harilaos
authors.initials: H
authors.lastname: Bogossian
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, Ludenscheid, Germany.
authors.forename: Ilias
authors.initials: I
authors.lastname: Ninios
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, Ludenscheid, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bandorski
authors.affiliation: Department of Cardiology, Helios Klinikum Wuppertal, Wuppertal, Germany.|Department of Cardiology, Witten / Herdecke University, Witten, Germany.
authors.forename: Melchior
authors.initials: M
authors.lastname: Seyfarth
authors.affiliation: Orthopedics and Traumatology, University Clinic Patras, Patras, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Matzaroglou
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, Ludenscheid, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Lemke
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
authors.affiliation: Märkische Kliniken GmbH, Department of Cardiology and Angiology, Klinikum Lüdenscheid, Ludenscheid, Germany.|Department of Cardiology, Witten / Herdecke University, Witten, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zarse
authors.affiliation: Spine-Center, Asklepios Clinic Lindenlohe, Schwandorf, Germany.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kafchitsas
mesh_terms: D064591:Allografts; D000818:Animals; D003324:Coronary Artery Disease / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects* / Q000201:enzymology; D016572:Cyclosporine / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006084:Graft Rejection / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Cyclosporin A; Mycophenolate mofetil; NO-Synthase; Rat Cardiac Allograft; Tacrolimus; Transplant Vasculopathy