Endothelin and endothelin A/B receptors are increased after ischaemic acute renal failure

Background/Aims: Endothelin (ET) has been implicated as an indirect mediato r of injury following acute renal ischaemia (ARI). The purpose of this stud y was to localize and quantitate ET and ETA and ETB receptors following ARL Methods: A model of ARI, well characterized previously, was produced by 45 min occlusion of the renal pedicle of unilaterally nephrectomized female S prague-Dawley rats. Animals were sacrificed 1, 2, 4, 8, 16, 32 and 64 days after ischaemia (n = 6). Corresponding control groups with unilateral nephr ectomy but no ischaemia were sacrificed after 0, 8 and 64 days. Immunohisto chemistry for ET-1, -2 and -3 was performed. Tissue ET levels were calculat ed by RIA (femtomoles per kidney). Receptor ligand binding studies for ETA and ETB receptors were performed by autoradiography on frozen kidney sectio ns and quantitated by densitometry (relative optical density per square mil limetre). Results: The concentration of tissue ET increased from 24 h after ischaemia and remained significantly increased for the duration of the stu dy, reaching a maximum at 8 days. There was a small increase in the non-isc haemic 8-day control group, but this returned to basal levels by day 64. Th e increase in tissue ET 8 days after ischaemia was localized by immunohisto chemistry to renal medullary interstitial cells, damaged tubules at the cor ticomedullary junction and peritubular capillaries surrounding these damage d tubules. Increases in cortical ETA and ETB receptors were evident 24 h af ter ischaemia and were maximal 8 days after ischaemia, before returning to basal levels at 16 days. After a small increase 24 h after ischaemia, medul lary ETA receptors decreased on day 4 before returning to basal levels on d ay 8 after ischaemia. Medullary ETB receptors, however, decreased on day 4 after ischaemia and remained low throughout the duration of the study. Conc lusion: The previously reported amelioration of pathological changes result ing from the use of ET receptor antagonists after ARI may be related to the quantitative and qualitative changes in tissue ET and ET receptors observe d in this study. Copyright (C) 2001 S. Karger AG, Basel.