Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats

Sharon R. Inman, Wanda K. Plott, Ray A. Pomilee, Jodi A. Antonelli, Richard M. Lewis

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15 Scopus citations


Background. 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). Methods. 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 ETA/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. Results. 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). Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)1655-1659
Number of pages5
Issue number10
Publication statusPublished - May 27 2003


ASJC Scopus subject areas

  • Transplantation
  • Immunology

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