Increased renal endothelin formation is associated with sodium retention and increased free water clearance.
To investigate whether renal endothelin (ET)-1 participates in water and sodium handling, we investigated the influence of different sodium intakes on renal production of ET-1 in eight healthy subjects. The functional relationship with the renin-angiotensin system was also studied. 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 expression for preproendothelin-1 in epithelial cells of medullary collecting ducts and endothelial cells of the peritubular capillary network. Increased ET-1 renal synthesis was associated with sodium retention and increased free water clearance. Urinary ET-1 excretion changes from normal to low-sodium diet were negatively related to contemporary changes in sodium excretion (r = 0.97, P < 0.05) and were positively correlated with free water clearance (r = 0.97, P < 0.05). These correlations were maintained during angiotensin-converting enzyme inhibition, which only partially reduced ET-1 renal excretion. These results indicate that renal ET-1 production is indeed modulated by varying sodium intakes and may exert a role in sodium and water handling.
Modesti
P A
PA
Clinica Medica Generale e Cardiologia, University of Florence, 50134 Florence, Italy.
Cecioni
I
I
Migliorini
A
A
Naldoni
A
A
Costoli
A
A
Vanni
S
S
Serneri
G G
GG
D000328:Adult; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001834:Body Water / Q000378:metabolism*; D004039:Diet, Sodium-Restricted; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000652:urine; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009318:Natriuresis; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism*; D012982:Sodium, Dietary / Q000008:administration & dosage
D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D011498:Protein Precursors; D012333:RNA, Messenger; D012982:Sodium, Dietary; D000803:Angiotensin I; D012964:Sodium; D012083:Renin; D017257:Ramipril