BQ-123, A SPECIFIC ENDOTHELIN (ET(A)) RECEPTOR ANTAGONIST, PREVENTS ISCHEMIA-REPERFUSION INJURY IN KIDNEY-TRANSPLANTATION

We studied the effects of the specific endothelin (ET(A)) receptor ant agonist, BQ-123, on reperfusion injury in a rat model of kidney transp lantation. First, Sprague-Dawley rats were divided into three groups: a sham nephrectomy (SNEPH), an autotransplantation (AUTO-Tx), and an a llotransplantation (ALLO-Tx) group. In a fourth group, ALLO-Tx + BQ, a llografts were flushed with 20 mu g BQ-123 containing cold Ringer's la ctate before transplantation. For the allograft groups, kidneys from w hite Wistar albino rats were transplanted into allogeneic Sprague Dawl ey recipients. Grafts were allowed 120 min of reperfusion after 40 min of cold ischemia. ET-1,2 plasma concentrations in the renal venous bl ood, and kidney tissue prostaglandin (PG) E(2) and leukotriene (LT) B- 4 levels were studied. Diene conjugates (DC), hydroxyalkanals (HAA), h ydroxyalkenals (HAE) and malondialdehyde (MDA) levels, as the products of lipid peroxidation, and protein carbonyls (PC) and protein sulphyd ryls (PS), as the parameters of protein oxidation, were also analyzed in the kidney tissue. Plasma ET concentrations increased significantly in the AUTO-Tx and ALLO-Tx groups (P < 0.05 and P < 0.01, respectivel y) but this increase was reversed in the ALLO-Tx + BQ group. None of t he lipid peroxidation products except DCs (P < 0.05) increased in the AUTO-Tx group, whereas they all increased in the ALLO-Tx group (P < 0. 01). Protein oxidation parameters also changed significantly (P < 0.01 ) in the ALLO-Tx group but did not in the AUTO-Tx group (P < 0.05). Th e differences in PGE(2) and LTB(4) levels were not significant. Histop athologic examination revealed prominent glomerular and tubular injury in the AUTO-Tx and ALLO-Tx groups but less in the ALLO-Tx + BQ group. In the last group, all parameters of lipid peroxidation (P < 0.001 fo r all) and PCs decreased, and PSs were preserved (P < 0.001 for both) when compared with the AUTO-Tx and ALLO-Tx groups. We conclude that BQ -123, in addition to inhibiting the binding of ET-1,2 to the ET(A) rec eptor, may also inhibit the release and/or synthesis of ET-1,2 and pre vent reperfusion injury in kidney transplantation.