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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Endothelin Receptor Antagonists, Glomerular Filtration Rate, Ischemia, Kidney, Kidney Diseases, Kidney Transplantation, Nephrectomy, Postoperative Period, Pyrrolidines, Rats, Rats, Inbred Lew, Renal Circulation, Sulfonamides.
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Does endothelin-receptor blockade mitigate the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats? Context: Ischemia-reperfusion injury has been established as a nonimmunologic risk factor for the development of chronic graft nephropathy after renal transplantation. This objective of this study was to determine if oral administration of an endothelin-1 receptor (ET-R) antagonist over a 2-month period after renal transplantation would mitigate long-term dysfunction associated with 30 min of preretrieval warm ischemia (pre-WI). The left kidney was retrieved from 250-g Lewis rats. Recipients underwent left nephrectomy and isografting using standard techniques. Animals were divided into three groups: nonischemic controls (no pre-WI, n=8); ischemic controls (pre-WI only, n=6); and pre-WI kidneys in which recipients received the ET(A/B) receptor antagonist, A182086, daily (30 mg/kg/day) (pre-WI/ET-R antagonist, n=6). Isograft glomerular filtration rate (GFR) was measured at 2 months. Measurement of GFR (mL/min) were as follows: no pre-WI, 2.1+/-0.26; pre-WI only, 1.24+/-0.14 (P<0.05 vs. no pre-WI); and pre-WI/ET-R antagonist, 2.3+/-0.45 (P<0.05 vs. pre-WI only and P=NS vs. no pre-WI).
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Chronic administration of a nonselective ET-R antagonist given after the ischemic insult, mitigated the decline in GFR at 2 months. These observations provide an experimental rationale for further investigation of the potential long-term protective effect of nonselective ET-R blockade versus ischemia-reperfusion injury in the clinical setting. Final Decision: yes