DIRECT VASCULAR EFFECTS IN THE RAT OF THE VEHICLES USED FOR THE INTRAVENOUS AND ORAL-ADMINISTRATION OF CYCLOSPORINE-A

1. The contraction and relaxation responses to the polyoxyethylated vehicles currently used for the intravenous and oral administration of cyclosporin A in allograft recipients were studied in isolated rat aorta. The results were compared with those obtained with commercially available cyclosporin A for intravenous administration. 2. None of these compounds affected resting tension, noradrenaline-induced contraction or endothelium-independent relaxation produced by sodium nitroprusside or bumetamide. However, they all reversed the relaxation induced by acetylcholine, carbamylcholine or adenosine 5'-triphosphate, by a factor of approximately 66%. 3. This reversal of relaxation was unaffected by indomethacin and did not require the presence of cyclosporin A in the vehicles, and was completely abolished by L-arginine (3 x 10-5 mol/l). 4. It is concluded that vehicles used for commercial preparations of cyclosporin A interfere with the synthesis of endothelium-derived relaxing factor at an early stage during which L-arginine is made available for enzymatic degradation.