Endothelin ET_A and ET_B receptor antagonism during cold preservation in renal transplantation

Background. In this study, we investigated the effects of selective endothelin (ET) receptor antagonism during different periods of cold ischemia on glomerular and tubular function and long-term survival in renal transplantation. Methods. Left renal transplantation was performed in Lewis rats after 2 hr of cold ischemia without (n=8) and with (n=6) ET_A receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ET_A receptor antagonism (n=8) and with ET_B receptor antagonism (n=6). A control group (n=8) underwent right nephrectomy and left renal denervation. The ET_A and ET_B receptor antagonists (BQ-610 and A-192621, respectively) were added to the preservation solution (EuroCollins). After transplantation, renal glomerular and tubular functions were monitored for up to 60 days or death. Results. All animals in the control and 2-hr groups survived the follow-up protocol, with early postoperative recovery of glomerular and tubular function while the entire untreated 16-hr group died between day 3-6 postoperatively. BQ-610 treatment had no measurable effect on the renal function in the 2-hr group, however, it improved glomerular and tubular functions and led to 50% long-term survival (60 days) in the 16-hr group. A-192621 treatment had no effect on long-term survival or renal parameters. Conclusion. ET_A receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ET_B receptor antagonism had not.