New vasoactive peptides in cirrhosis: organ extraction and relation to the vasodilatory state.
BACKGROUND
Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations to haemodynamic changes in the pro-peptides copeptin, proadrenomedullin and pro-atrial natriuretic peptide (proANP) in patients with cirrhosis.


METHODS
Fifty-four cirrhotic patients and 15 controls were characterized haemodynamically during a liver vein catheterization. Copeptin, proadrenomedullin and proANP were measured in hepatic and renal veins and the femoral artery.


RESULTS
We found no differences in concentrations of copeptin and proadrenomedullin between patients and controls. ProANPs were higher in cirrhotic patients, median 138 pm (25/75 percentiles 101-194) compared with controls, median 91 pm (25/75 percentiles 82-153) P=0·02. ProANPs were higher in the femoral artery and renal vein, median 140 pm and 116 pm (25/75 percentiles 109-191 and 92-164, respectively), compared with controls, median 99 and 81 (25/75 percentiles 85-146 and 66-123) P=0·02 and P=0·007, respectively. We found no extraction of copeptin, proadrenomedullin or proANP over the liver. Copeptin correlated with portal pressure (R=0·50, P<0·001). Proadrenomedullin correlated with portal pressure (R=0·48, P<0·001) and heart rate (R=0·36, P<0·01). ProANP correlated with cardiac output (R=0·46, P<0·002) and portal pressure (R=0·32, P<0·02). All propeptides correlated with Child score (R>0·31, P<0·03).


CONCLUSIONS
Pro-atrial natriuretic peptide is elevated in cirrhosis. Copeptin, proadrenomedullin and proANP are related to portal pressure and seem associated with systemic haemodynamics. These propeptides may participate in development and perpetuation of vasodilatation and hyperdynamic circulation in cirrhosis.
Department of Clinical Physiology and Nuclear Medicine, Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
Nina
N
Kimer
Jens Peter
JP
Goetze
Flemming
F
Bendtsen
Søren
S
Møller
D053607:Adrenomedullin / Q000378:metabolism*; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005263:Femoral Artery / Q000378:metabolism; D006020:Glycopeptides / Q000378:metabolism*; D006503:Hepatic Veins / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism*; D012082:Renal Veins / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology
D006020:Glycopeptides; D011498:Protein Precursors; C048197:copeptins; C088633:proadrenomedullin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor
Cirrhosis; copeptin; haemodynamics; portal hypertension; proadrenomedullin; proatrial natriuretic peptide