NDT Advance Access published online on August 24, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh471
© 2004 by European Renal Association - European Dialysis and Transplant Association
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Nephrology and Hypertension, University Medical Center Utrecht, the Netherlands
* To whom correspondence should be addressed. E-mail: 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.
Accepted June 2, 2004
Original Papers
Effects of endothelin-1 and endothelin-1-receptor blockade on renal function in humans
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Cottone, G. Mule, M. Guarneri, A. Palermo, M. C. Lorito, R. Riccobene, R. Arsena, F. Vaccaro, A. Vadala, E. Nardi, et al. Endothelin-1 and F2-isoprostane relate to and predict renal dysfunction in hypertensive patients Nephrol. Dial. Transplant., February 1, 2009; 24(2): 497 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Battistini, N. Berthiaume, N. F. Kelland, D. J. Webb, and D. E. Kohan Profile of Past and Current Clinical Trials Involving Endothelin Receptor Antagonists: The Novel "-Sentan" Class of Drug. Experimental Biology and Medicine, June 1, 2006; 231(6): 653 - 695. [Abstract] [Full Text] [PDF]
|
|