The role of endothelin in early renal cortical reperfusionin renal transplantation.
The role of specific endothelin receptors in the early renal reperfusion and long-term survival in renal transplantation was investigated in Lewis rats. Left renal transplantation was performed following 2 h cold ischaemia without and with ET(A) receptor antagonism and following 16 h cold ischaemia with no treatment, with ET(A) receptor antagonism and with ET(B) receptor antagonism. The ET(A) and ET(B) receptor antagonists, BQ-610 and A-192621 respectively, were added to the preservation solution. Renal cortical perfusion (RCP) was measured postoperatively using laser Doppler flowmetry. All rats in the 2-hour groups survived for 15 days. Animals in the untreated 16-hour group or in the A-192621-treated group died between days 3 and 6 after surgery. Fifty percent of the rats in the 16-hour and BQ-610-treated group died between days 4 and 7 after surgery while the other 50% survived for 15 days. Survival rates correlated well with both the postoperative serum creatinine and the recovery of RCP. We conclude that addition of an ET(A) receptor antagonist to the preservation solution improves renal reperfusion and long-term survival following prolonged ischaemia, whereas ET(B) receptor antagonism does neither.
Hammad
F T
FT
Microcirculation Research Laboratory, Department of Physiology, School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Davis
G
G
Zhang
X
X
Wheatley
A M
AM
D000818:Animals; D003080:Cold Temperature; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D007672:Kidney Cortex / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries; D016030:Kidney Transplantation / Q000009:adverse effects / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D009926:Organ Preservation; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology
C120508:A 192621; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C087220:BQ 610