In order to investigate the role of
endothelin in the pathogenesis of ARF, we determined the plasma
endothelin (pET) level in different clinical ARF patients and experimental ARF rat models. It was found that pET level was significantly higher in hepatic renal syndrome (n = 9, pET 210.1 +/- 32.0 pg/ml),
epidemic hemorrhagic fever (n = 18, 113.3 +/- 14.86 pg/ml),
septic shock ARF (n = 8, 121.5 +/- 13.5 pg/ml),
gentamicin ARF (n = 7, 55.9 +/- 6.23 pg/ml) patients, and in
HgCl2 ARF (n = 8, 31.75 +/- 3.07 pg/ml),
glycerine ARF (n = 8, 44.75 +/- 9.8 pg/ml) rats, compared with that of normal persons (n = 9, 33.6 +/- 3.08 pg/ml) or of normal rats (n = 10, 11.4 +/- 0.98 pg/ml). Both in the patients and animal groups, there were a linear relationship between the levels of pET and Scr (r = 0.603 4 and 0.844, P less than 0.01, respectively). Intrarenal infusion ET in dosage of 0.16 micrograms.kg-1/h produced a severe reduction of RPF and GFR in the infused kidney, without significant similar changes on the contralateral kidney. Pretreated with
captopril ameliorated the renal hemodynamic changes induced by iv ET (0.67 micrograms.kg-1/h), whereas
indomethacin potentiated this effect. It is concluded that both circulating or local generated ET during the ARF play an important role in the pathogenesis of ARF. RAS and PG might involve in its mechanisms.