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) ETA receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ETA receptor antagonism (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 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: ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.
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) ETA receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ETA receptor antagonism (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 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:ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.
Authors: Fayez T Hammad; Suhail Al-Salam; Sarah S AlZaabi; Maryam M Alfalasi; Awwab F Hammad; Javed Yasin; Loay Lubbad Journal: Physiol Rep Date: 2021-03