Expression of NO Synthase Under Medication with Cyclosporine A, Mycophenolate Mofetil, and Tacrolimus during Development of Transplant Vasculopathy on Rat Cardiac Allograft

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. Aims: 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.