Pa. Modesti et al., INCREASED RENAL ENDOTHELIN FORMATION IS ASSOCIATED WITH SODIUM RETENTION AND INCREASED FREE-WATER CLEARANCE, American journal of physiology. Heart and circulatory physiology, 44(3), 1998, pp. 1070-1077
To investigate whether renal endothelin (ET)-1 participates in water a
nd sodium handling, we investigated the influence of different sodium
intakes on renal production of ET-1 in eight healthy subjects. The fun
ctional relationship with the renin-angiotensin system was also studie
d. Renal ET-1 formation is affected by sodium intake, because 1 wk of
high sodium decreased urinary ET-1 excretion (-34%, P < 0.05), whereas
a low-sodium diet increased ET-1 excretion (66%, P < 0.05) and mRNA e
xpression for preproendothelin-l in epithelial cells of medullary coll
ecting ducts and endothelial cells of the peritubular capillary networ
k. Increased ET-1 renal synthesis was associated with sodium retention
and increased free water clearance. Urinary ET-1 excretion changes fr
om normal to low-sodium diet were negatively related to contemporary c
hanges in sodium excretion (r = 0.97, P < 0.05) and were positively co
rrelated with free water clearance (r = 0.97, P < 0.05). These correla
tions were maintained during angiotensin-converting enzyme inhibition,
which only partially reduced ET-1 renal excretion. These results indi
cate that renal ET-1 production is indeed modulated by varying sodium
intakes and may exert a role in sodium and water handling.