Endothelin-1 (ET-1) is a 21-amino acid peptide that potently modulates
renal function. ET-1 is produced by, and binds to, most renal cell ty
pes. ET-1 exerts a wide range of biologic effects in the kidney, inclu
ding constriction of most renal vessels, mesangial cell contraction, i
nhibition of sodium and water reabsorption by the nephron, enhancement
of glomerular cell proliferation, and stimulation of extracellular ma
trix accumulation. ET-1 functions primarily as an autocrine or paracri
ne factor; its renal effects must be viewed in the context of its loca
l production and actions. This is particularly important when comparin
g ET-1 biology in the nephron, where it promotes relative hypotension
through increased salt and water excretion, with ET-1 effects in the v
asculature, where it promotes relative hypertension through vasoconstr
iction. Numerous studies indicate that ET-1 is involved in the pathoge
nesis of a broad spectrum of renal diseases. These include those chara
cterized by excessive renal vascular resistance, such as ischemic rena
l failure, cyclosporine (CyA) nephrotoxicity, radiocontrast nephropath
y, endotoxemia, rhabdomyolysis, acute liver rejection, and others, ET-
1 appears to play a role in cell proliferation in the setting of infla
mmatory glomerulonephritides. The peptide also may mediate, at least i
n part, excessive extracellular matrix accumulation and fibrosis occur
ring in chronic renal failure, diabetes mellitus, and other disorders,
Deranged ET-1 production in the nephron may cause inappropriate sodiu
m and water retention, thereby contributing to the development and/or
maintenance of hypertension, Finally, impaired renal clearance of ET-1
may cause hypertension in patients with end-stage renal disease. Many
ET-1 antagonists have been developed; however, their clinical usefuln
ess has not yet been determined, Despite this, these agents hold great
promise for the treatment of renal diseases; it is hoped that the nex
t decade will witness their introduction into clinical practice. (C) 1
997 by the National Kidney Foundation, Inc.