Daily profile of plasma endothelin-1 and -3 in pre-ascitic cirrhosis: relationships with the arterial pressure and renal function.
OBJECTIVE
Measurements of plasma endothelin-1 and -3 in pre-ascitic cirrhosis have provided controversial results. Similarly, the role of the endothelin system in the pathogenesis of volume and hemodynamic disturbances of cirrhosis is still debated. To provide a further insight into this issue, we assessed the daily fluctuations of plasma endothelins and their relationship with arterial pressure and renal function in pre-ascitic cirrhosis.


METHODS
Endothelin-1 and -3, plasma renin activity, atrial natriuretic peptide, noradrenaline and mean arterial pressure were measured at 11 pm, 7 am, 9 am and 6 pm in 10 patients with pre-ascitic cirrhosis and in 10 healthy subjects on normal sodium diet and carrying on their usual activities (supine from 10 pm to 7 am, standing and mobile after 7 am). Glomerular filtration rate and daily renal sodium excretion were assessed during the supine period, and from 7 am to 12 am and from 12 am to 10 pm during the standing period.


RESULTS
Endothelin-1 was higher in patients than in control subjects (p=0.000) and did not change during the study. Endothelin-3 was also higher in patients (p=0.002) and showed slight fluctuation in control subjects. The mean daily level of plasma renin activity was lower (p=0.016) and that of atrial natriuretic peptide higher (p=0.000) in patients with cirrhosis. Norepinephrine and mean arterial pressure did not differ significantly between the two groups. No correlations were found between endothelins and either hemodynamic or neuro-hormonal and renal function parameters in the two groups.


CONCLUSIONS
Despite the presence of increased effective volemia (as suggested by the reduced plasma renin activity and elevated atrial natriuretic peptide) and normal adrenergic tone, patients with pre-ascitic cirrhosis show elevated levels of endothelin-1 and endothelin-3 throughout the day. In early cirrhosis circulating endothelins, although elevated, do not appear to play a more prominent role in setting arterial pressure than in normal subjects, and endothelin elevation is not detrimental to renal function.
Trevisani
F
F
Department of Internal Medicine, Cardioangiology, Hepatology, University of Bologna, Italy.
Colantoni
A
A
Gerbes
A L
AL
Gülberg
V
V
Sica
G
G
Caraceni
P
P
De Notariis
S
S
Morselli-Labate
A M
AM
Ligabue
A
A
Gasbarrini
G
G
Bernardi
M
M
D000328:Adult; D000368:Aged; D001201:Ascites / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure; D002940:Circadian Rhythm; D019332:Endothelin-1 / Q000097:blood*; D019334:Endothelin-3 / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009318:Natriuresis; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood
D019332:Endothelin-1; D019334:Endothelin-3; D009320:Atrial Natriuretic Factor; D012083:Renin; D009638:Norepinephrine