The Role of Endothelin inEarly Renal Cortical Reperfusionin Renal Transplantation

Abstract

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.

Correlation between endothelin expression in early post‐transplant biopsy specimens and long‐term allograft function in living‐related renal transplantation

“…We examined ET immunoreactivity in biopsy specimens at 3M after transplantation, correlating ET expression with change in graft function between 3M and 3Y after transplantation. As a caderveric donor kidney is subjected to varying degrees of warm and cold ischemia causing ischemia – reperfusion injury that may lead to acute tubular necrosis (9), we excluded caderveric grafts from study.…”

“…All isoforms are products of cleavage of specific prohormones. Prepro‐ET is cleaved to form big‐ET, which in turn is converted by proteases into peptides 21 amino acids in length; the most abundant of these is ET‐1 (8–11). Synthesized by vascular endothelial cells (6, 12), renal mesangial cells (13, 14), glomerular endothelial cells (15) and tubular epithelial cells (16, 17), ET‐1 is well positioned to cause changes in renal vascular tone, particularly cortical vasoconstriction causing reduced renal blood flow and glomerular filtration rate (5, 15).…”

Role of Endothelin ETA Receptor Antagonism in the Post‐Transplant Renal Response to Angiotensin II in the Rat

“…For instance, BQ-123, a selective ET A receptor antagonist, was shown to attenuate the fall in GFR associated with 45 min of renal ischaemia in uninephrectomised rats (Gellai et al 1994). Recently, we have shown that ET A receptor antagonism with BQ-610 during hypothermic preservation improved early post-transplant renal cortical perfusion, renal function and long-term survival (Hammad et al 2000b). …”

“…Recently, we have shown that ET A receptor antagonism with BQ-610 during hypothermic preservation improved early post-transplant renal cortical perfusion, renal function and long-term survival (Hammad et al 2000b).…”

Endothelin Receptor Down-Regulation Mediated Ligand Regulation Mechanisms Protect Against Cellular Hypoxia Injury in Rat Vascular Endothelial Cells

“…Studies have indicated that nonselective endothelin receptor antagonist effectively normalized renal function in diabetic nephropathy [8]. However, blocking both ET A R and ET B R caused long-term renal dysfunction in IRI model [9]. As a result, inhibition of ETaR expression is considered a novel method in the treatment of renal ischemia reperfusion injury.…”