THE EFFECT OF CYCLOSPORINE ON ENDOTHELIN LEVELS AFTER ORTHOTOPIC LIVER-TRANSPLANTATION IN RATS

To assess the effects of cyclosporin (CyA) on endothelin-1 (ET-1) in r at liver allograft rejection, we evaluated ET-1 expression in samples obtained from BN(RT1(n))-to-BN (group 1) rats, DA(RT1(a))-to-BN (group 2) rats, and DA-to-BN rats treated with 5 mg/kg per day of CyA (group 3). Serum and hepatic ET-1 levels, determined by a radioimmunoassay, remained unchanged in group 1. In group 2, the ET-1 levels peaked on p ostoperative day (POD)5 in the liver at 344 +/- 31.6 pg/g wet, and on POD 7 in the serum at 38.7 +/- 13.1 pg/ml. In group 3, hepatic and ren al ET-1 levels showed a progressive increase until POU 10, while serum ET-1 levels remained unchanged. In conclusion, acute rejection caused a temporary increase in the ET-1 level in both the serum and the live r in the early postoperative period what might have been caused by end othelial damage due to ongoing, acute rejection. CyA caused a time-dep endent increase in the ET-1 level in both the liver and the kidney wit hout an increase in the serum ET-1 level. The serum ET-1 level might h ave been affected by the clearance of ET from the liver or kidney.