Role of endothelin ETA receptor antagonism in the post-transplant renal response to angiotensin II in the rat

The role of endothelins in the renal damage associated with ischaemic-reper fusion (I-R) injury during organ transplantation was determined by selectiv e blockade of the ETA receptors with the receptor antagonist ABT-627, The i ntegrity of kidney function was determined 2 and 8 weeks after transplantat ion by investigation of the renal response to angiotensin II. Under pentoba rbitone anaesthesia (70 mg kg(-1), I.P.), rats underwent a right nephrectom y, Transplantation of the left kidney was performed after 2 h cold ischaemi a without or,vith ABT-627 treatment. Control animals underwent left renal d enervation, The renal response to angiotensin II was measured 2 weeks later following blockade of endogenous production of angiotensin II with captopr il. A further transplant group was allowed to recover for 8 weeks before th e terminal study. In the control group, angiotensin II reduced renal blood now (RBF), glomerular filtration rate (GFR), urine now rate (UV), and fract ional sodium excretion (FENa) by 29 +/-5%, 19 +/-4%, 25 +/-4% and 32 +/-7%, respectively. Conversely, in the transplant group, angiotensin II left RBF unchanged and increased GFR (59 +/- 12 %) and UV (93 +/-8%), Fe-Na decreas ed by 24 +/-9%, In both the transplant group treated with ABT-627 and the l ong-term recovery group, the renal response to angiotensin II was normalise d, In conclusion, renal transplantation following 2 h cold I-R injury resul ted in a temporary abnormal renal response to angiotensin II, which was rev ersed by ETA receptor antagonism at the time of transplantation.