Renal endothelin in heart failure and its relation to sodium excretion

Background Recent studies have shown that endothelin-1 (ET-1) antagonists increase sodium excretion and improve renal blood flow in experimental heart failure (HF). However, despite a number of investigations that have reported a significant increase in ET-1 plasma levels in patients with HF, it 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 relation to sodium excretion in patients with HF. Methods One hundred forty-seven patients with HF, subdivided according to New York Heart Association (NYHA) functional classes, and 28 healthy controls were studied. ET-1 and big ET-1 were measured in plasma and in 24-hour urine by radioimmunoassay. Atrial and brain natriuretic peptide, arginine vasopressin, plasma renin activity, and hemodynamic variables were also investigated. Results Urinary ET-1 excretion was already increased in NYHA class II patients (P < .001 vs controls), whereas plasma ET-1 increased only in NYHA class 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 of 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, indicating renal ET-1 is a target for ET-1 antagonists in patients with HF. (Am Heart J 2000;140:617-23.)