Role of endothelin ET_A 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-reperfusion (I-R) injury during organ transplantation was determined by selective blockade of the ET_A receptors with the receptor antagonist ABT-627. The integrity of kidney function was determined 2 and 8 weeks after transplantation by investigation of the renal response to angiotensin II. Under pentobarbitone anaesthesia (70 mg kg^-1, I.P.), rats underwent a right nephrectomy. Transplantation of the left kidney was performed after 2 h cold ischaemia without or with ABT-627 treatment. Control animals underwent left renal denervation. The renal response to angiotensin II was measured 2 weeks later following blockade of endogenous production of angiotensin II with captopril. A further transplant group was allowed to recover for 8 weeks before the terminal study. In the control group, angiotensin II reduced renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (UV), and fractional sodium excretion (FE_Na) 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 decreased by 24 ± 9%. In both the transplant group treated with ABT-627 and the long-term recovery group, the renal response to angiotensin II was normalised. In conclusion, renal transplantation following 2 h cold I-R injury resulted in a temporary abnormal renal response to angiotensin II, which was reversed by ET_A receptor antagonism at the time of transplantation.