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.
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: Katrin Splith; Peter Fellmer; Ivan Matia; Martin Varga; Martin Oliverius; Stephanie Kuhn; Linda Feldbrügge; Felix Krenzien; Hans-Michael Hau; Georg Wiltberger; Moritz Schmelzle; Sven Jonas Journal: PLoS One Date: 2014-03-11 Impact factor: 3.240
Authors: Bassam G Abu Jawdeh; Anthony C Leonard; Yuvraj Sharma; Swapna Katipally; Adele R Shields; Rita R Alloway; E Steve Woodle; Charuhas V Thakar Journal: Front Med (Lausanne) Date: 2017-05-26
Authors: Rudolf Spunda; Jan Hruby; Pavel Mericka; Mikulas Mlcek; Ondrej Pecha; Kathrin Splith; Moritz Schmelzle; Felix Krenzien; Jaroslav Lindner; Ivan Matia; Miroslav Spacek Journal: PLoS One Date: 2018-08-09 Impact factor: 3.240
Authors: Arthur D Moes; David Severs; Koen Verdonk; Nils van der Lubbe; Robert Zietse; A H J Danser; Ewout J Hoorn Journal: Front Physiol Date: 2018-05-18 Impact factor: 4.566