title: Endotelin ETA and ETB receptor antagonism during cold preservation in renal transplantation.
abstract: 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.
  
  
  CONCLUSIONS
  ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.
authors: Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: F T
authors: FT
authors: Hammad
authors: G
authors: G
authors: Davis
authors: X Y
authors: XY
authors: Zhang
authors: A M
authors: AM
authors: Wheatley
mesh_terms: D000818:Animals; D015925:Cryopreservation; D065128:Endothelin Receptor Antagonists; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000503:physiopathology; D016030:Kidney Transplantation / Q000401:mortality; D007684:Kidney Tubules / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D012016:Reference Values; D016019:Survival Analysis; D013997:Time Factors
chemical_list: C120508:A 192621; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087220:BQ 610