Effect of an endothelin-receptor antagonist on ischemic acute renal failure

In the isolated perfused rat kidney, endothelin (ET) added to the perfusate at concentrations ranging from 50 to 500 pmol/l resulted in a dose-dependent reduction in renal perfusate flow (RPF) and inulin clearance (CIn). The decrease in RPF (17 +/- 3 vs. 34 +/- 3 ml.min-1 x g-1; P < 0.01 compared with control) and CIn (89 +/- 13 vs. 317 +/- 19 microliters.min-1 x g-1; P < 0.01 compared with control) by ET (500 pmol/l) was prevented by the ET antagonist BQ-123 (10 microM), with full recovery of RPF [36 +/- 2 vs. 34 +/- 3 ml.min-1 x g-1; not significant (NS) compared with control] and CIn (299 +/- 51 vs. 317 +/- 19 microliters.min-1 x g-1; NS compared with control). In the absence of ET, perfusion of the kidney with a similar concentration of BQ-123 (10 microM) did not induce any changes in RPF (36 +/- 5 vs. 34 +/- 3 ml.min-1 x g-1; NS compared with control) or CIn (320 +/- 14 vs. 317 +/- 19 microliters.min-1 x g-1; NS compared with control). After 60 min of arterial clamping, BQ-123 (10 microM) given before the onset of ischemia and during reflow improved CIn (88 +/- 4 vs. 19 +/- 3 microliters.min-1 x g-1; n = 6, P < 0.01) and net tubular sodium reabsorption (TNa) compared with no treatment. On the other hand, the same dose (10 microM) of BQ-123 given only during the reperfusion period was not effective in preventing the decreases in either CIn or TNa.(ABSTRACT TRUNCATED AT 250 WORDS)