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NDT Advance Access originally published online on August 24, 2004
Nephrology Dialysis Transplantation 2004 19(11):2742-2746; doi:10.1093/ndt/gfh471
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Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved

Original Article

Effects of endothelin-1 and endothelin-1-receptor blockade on renal function in humans

J. L. Tycho Vuurmans, Peter Boer and Hein A. Koomans

Department of Nephrology and Hypertension, University Medical Center Utrecht, the Netherlands

Correspondence and offprint requests to: Dr Peter Boer, PhD, Department of Nephrology and Hypertension, University Medical Center Utrecht, Room F03.226, PO Box 85500, 3805 GA Utrecht, the Netherlands. Email: p.boer{at}azu.nl

Background. In patients with renal or cardiac failure, renal function may be endangered by elevated plasma concentrations of the vasoconstrictor endothelin-1 (ET-1). To mimic effects of pathologically increased plasma ET-1, we gave intravenous ET-1 in healthy subjects and examined whether simultaneous infusion of the ETA-receptor antagonist VML 588 would prevent the effects of ET-1 on the kidney.

Methods. Nine healthy men received on four separate days intravenous infusion of ET-1 (2.5 ng/kg/min) superimposed on vehicle (saline) or on VML 588 infusion (0.05, 0.20 and 0.40 mg/kg/h) in randomized order to assess the effects on renal function and renal haemodynamics.

Results. At resting plasma ET-1, infusion of VML 588 alone had no significant effects on renal function. Infusion of ET-1 alone decreased glomerular filtration rate by 11% and this reduction was not reversed by co-infusion of VML 588. ET-1 reduced renal blood flow by 35% and VML 588 reduced this decrease by one-third, in a dose-independent fashion. ET-1 increased the filtration fraction by 34% and VML 588 reduced this increase dose-independently by one-half. ET-1 increased renal vascular resistance by 59% and VML 588 reduced this increase dose-independently by one-half. Finally, ET-1 decreased sodium excretion by 58% and VML 588 reduced this decrease dose-independently by two-thirds.

Conclusions. ET-1-induced reductions in renal function were partially but not completely prevented in a dose-independent manner by the ETA-receptor antagonist VML 588.

Keywords: endothelin-1; endothelin-1-receptor antagonist; filtration fraction; glomerular filtration rate; renal blood flow; renal vascular resistance


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