Urinary endothelin: a possible biological marker of renal damage

Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and secreted by the vascular endothelium. Significant amounts of ET are also produced by nonendothelial cells, mainly tubular-epithelial and mesangial cells. Large amounts of ET are found in the urine compared with the small amounts present in blood. Because most of the ET filtered from plasma is subject to degradation by neutral endopeptidase (EC 3.4.24.11) in the proximal tubule, urinary ET is probably of renal origin. The range of urinary ET excretion in healthy persons is 20 to 90 ng/day. The excretion of endothelin is modulated by several mechanical and chemical stimuli such as angiotensin II, phenylephrine, radiocontrast media, cyclosporine, and cis-platin. In addition, enhanced urinary ET excretion has been found in several forms of renal failure, both acute and chronic, and in diabetes mellitus. Thus, urinary ET has the potential of serving as a marker for renal disease.