Background. In this study, we investigated the effects of selective endothe
lin (ET) receptor antagonism during different periods of cold ischemia on g
lomerular and tubular function and long-term survival in renal transplantat
ion.
Methods. Left renal transplantation was performed in Lewis rats after 2 hr
of cold ischemia without (n=8) and with (n=6) ETA receptor antagonism and a
fter 16 hr of cold ischemia without treatment (n=6), with ETA receptor anta
gonism (n=8) and with ETB receptor antagonism (n=6). A control group (n=8)
underwent right nephrectomy and left renal denervation. The ETA and ETB rec
eptor antagonists (BQ-610 and A-192621, respectively) were added to the pre
servation solution (EuroCollins), After transplantation, renal glomerular a
nd 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 funct
ion while the entire untreated 16-hr group died between day 3-6 postoperati
vely, BQ-610 treatment had no measurable effect on the renal function in th
e 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. ETA receptor antagonism had protective renal effects after prol
onged ischemic preservation in renal transplantation while ETB receptor ant
agonism had not.