The use of the endothelin receptor antagonist, Tezosentan, before or afterrenal ischemia protects renal function

Background. Utilization of organs subjected to ischemia/reperfusion (VR) in jury could expand the donor pool. Endothelin (ET) is implicated in renal YR injury. Therefore, our study compared the effectiveness of pre- and postis chemic administration of the ET receptor antagonist, Tezosentan, in preserv ing renal function. Methods. In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy, After 24 hr of reperfusion, renal functi on was assessed by serum creatinine (Scr), inulin clearance (glomerular fil tration rate; GFR), and histology. ET-I peptide expression was localized us ing immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and YR posttreated (n=13) with Tezosentan (15 mg/kg, i.v.), Results. Tezosentan significantly decreased (P<0.05) the rise in Scr from T m,injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) com pared with untreated animals (4.2+/-0.4 mg/dl), GFR was significantly incre ased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 an d 0.47+/-0.14 ml/min (pre- and posttreated animals), Untreated animals had significant cortical acute tubular necrosis, which was almost completely pr e vented by pretreatment with Tezosentan and markedly reduced by posttreatm ent, Increased ET-1 peptide expression was noted in the renal vasculature a nd in the cortical tubular epithelium of kidneys exposed to I/R. Conclusions, The purpose of this study was to optimize the function of kidn eys exposed to I/R injury. Pretreatment as well as posttreatment with Tezos entan successfully decreased Scr, increased GFR, and maintained renal archi tecture in kidneys after ischemia, Therefore, ET receptor antagonists may b e useful to preserve renal function in the transplantation setting.