Renal endothelin in heart failure and its relation to sodium excretion

Background Recent studies have shown that endothelin-l (ET-1) antagonists i ncrease sodium excretion and improve renal blood flow in experimental heart Failure (HF). However, despite a number of investigations that have report ed a significant increase in ET-1 plasma levels in patients with HF, ii is still not known whether increased renal synthesis and urinary excretion of ET-1 occur, Our aim was to investigate renal ET-1 formation and its relatio n to sodium excretion in patients with HF. Methods One hundred forty-seven patients with HF, subdivided according to N ew York Heart Association (NYHA) functional classes, and 28 healthy control s were studied. ET-1 and big ET-1 were measured in plasma and in 24-hour ur ine by radioimmunoassay, Atrial and brain natriuretic peptide, arginine vas opressin, plasma renin activity, and hemodynamic variables were also invest igated. Results Urinary ET-I excretion was already increased in NYHA class II patie nts (P < .001 vs controls), whereas plasma ET-1 increased only in NYHA clas s III and IV patients (P < .001). In the 71 subjects who were not receiving diuretic treatment, urinary ET-1 was selected as the strongest predictor o f sodium excretion by multivariate stepwise analysis. Conclusions Urinary ET-1 excretion increases in an earlier phase of HF than plasma ET-1 and appears to be closely correlated with sodium excretion, in dicating renal ET-1 is a target for ET-1 antagonists in patients with HF.