title: Protective effect of mycophenolate mofetil on endothelial function in an aortic allograft model.
abstract: BACKGROUND
  Whether mycophenolate mofetil (MMF) can prevent the vascular endothelial dysfunction related to the administration of calcineurin inhibitor after organ transplantation remains unknown.
  
  
  METHODS
  Four groups of Lewis rats, grafted with Brown Norway donor aortic abdominal allograft, received since the transplantation cyclosporine A (CsA, 5 mg/kg/day), MMF (40 mg/kg/day), CsA+MMF, or vehicle (control) for 2 weeks.
  
  
  RESULTS
  Fifteen days after transplantation, all immunosuppressive regimens were equally effective in preventing graft rejection. When compared with control rats, the endothelium-dependent relaxation to acetylcholine was reduced, and the vasoconstrictor effect of phenylephrine was enhanced in thoracic aorta of CsA-treated rats but not in rats treated with MMF alone or combined with CsA without difference for the endothelium-independent relaxation to sodium nitroprusside. The relaxation to acetylcholine was abolished by the nitric oxide (NO)-synthase inhibitor N-nitro-l-arginine in all groups. Moreover, the endothelial NO-synthase protein dimer:monomer ratio in the thoracic aorta and the plasma nitrites concentrations, an indicator of NO availability, were decreased in CsA-treated rats but not in rats treated with MMF alone or combined with CsA.
  
  
  CONCLUSIONS
  This study demonstrates that MMF prevents systemic endothelial dysfunction and the enhanced sensitivity to vasoconstrictors related to CsA administration in a rat allograft aortic model through an increase in NO availability related to the improvement of endothelial NO-synthase functionality.
authors: Department of Nephrology and Hemodialysis, Rouen University Hospital, Rouen, France.
authors: Caroline
authors: C
authors: Fréguin-Bouilland
authors: Michel
authors: M
authors: Godin
authors: Jeremy
authors: J
authors: Bellien
authors: Vincent
authors: V
authors: Richard
authors: Isabelle
authors: I
authors: Remy-Jouet
authors: Brigitte
authors: B
authors: Dautreaux
authors: Jean-Paul
authors: JP
authors: Henry
authors: Patricia
authors: P
authors: Compagnon
authors: Christian
authors: C
authors: Thuillez
authors: Didier
authors: D
authors: Plissonnier
authors: Robinson
authors: R
authors: Joannidès
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000637:transplantation*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006084:Graft Rejection / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013113:Spin Labels; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D003497:Cyclic N-Oxides; D007166:Immunosuppressive Agents; D009573:Nitrites; D013113:Spin Labels; D009599:Nitroprusside; D019335:Nitroarginine; D016572:Cyclosporine; D019001:Nitric Oxide Synthase; D009173:Mycophenolic Acid; C001803:tempol