Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and
secreted by the vascular endothelium. Significant amounts of ET are al
so produced by nonendothelial cells, mainly tubular-epithelial and mes
angial cells. Large amounts of ET are found in the urine compared with
the small amounts present in blood. Because most of the ET filtered f
rom 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/d
ay. The excretion of endothelin is modulated by several mechanical and
chemical stimuli such as angiotensin IT, phenylephrine, radiocontrast
media, cyclosporine, and cis-platin. In addition, enhanced urinary ET
excretion has been found in several forms of renal failure, both acut
e and chronic, and in diabetes mellitus. Thus, urinary ET has the pote
ntial of serving as a marker for renal disease.