Endothelin antagonists in the treatment of renal failure

The degree to which ET-1 participates in the pathogenesis of renal dysfunction remains poorly understood. In the kidney, ET-1 not only produces vasoconstriction, but also vasodilation in the renal medulla, stimulation of sodium reabsorption in the proximal tubule, and inhibition of reabsorption in a variety of nephron segments. It is clear that ET-1 production is increased in most forms of renal failure, although the cause of this increase is not known. Endothelin receptor antagonists, as therapeutic agents, have been investigated in a large variety of animal models, and even though there have been some promising results, there are many conflicting reports. While there is little known about the therapeutic utility of endothelin receptor antagonists in human renal failure, progress is most likely to be slow due to the complex nature of ET-1 actions and the less than promising initial studies in humans.