Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats.
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 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. 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.
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- Surgery
- Sulfonamides
- Renal Circulation
- Rats, Inbred Lew
- Rats
- Pyrrolidines
- Postoperative Period
- Nephrectomy
- Kidney Transplantation
- Kidney Diseases
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Surgery
- Sulfonamides
- Renal Circulation
- Rats, Inbred Lew
- Rats
- Pyrrolidines
- Postoperative Period
- Nephrectomy
- Kidney Transplantation
- Kidney Diseases