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.
Modesti
P A
PA
Clinica Medica Generale e Cardiologia, University of Florence, Italy. pamodesti@dfe.unifi.it
Cecioni
I
I
Costoli
A
A
Poggesi
L
L
Galanti
G
G
Serneri
G G
GG
D000368:Aged; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002940:Circadian Rhythm; D018450:Disease Progression; D019332:Endothelin-1 / Q000097:blood / Q000652:urine*; D005260:Female; D006333:Heart Failure / Q000401:mortality / Q000503:physiopathology / Q000652:urine*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011379:Prognosis; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D012720:Severity of Illness Index; D012964:Sodium / Q000652:urine*; D015996:Survival Rate
D015415:Biomarkers; D019332:Endothelin-1; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin