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.