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)
Chan
L
L
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Chittinandana
A
A
Shapiro
J I
JI
Shanley
P F
PF
Schrier
R W
RW
D000042:Absorption / Q000187:drug effects; D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism; D007511:Ischemia / Q000150:complications*; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D015424:Reperfusion
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D007444:Inulin; C072247:cyclo(Trp-Asp-Pro-Val-Leu)