INCREASED ADRENOMEDULLIN LEVELS IN CIRRHOSIS - RELATIONSHIP WITH HEMODYNAMIC ABNORMALITIES AND VASOCONSTRICTOR SYSTEMS

Background & Aims: Arterial vasodilation in cirrhosis may be related t o increased circulating levels of vasodilators. This study was designe d to assess the circulating levels of adrenomedullin, a recently descr ibed vasodilator peptide, in cirrhosis. Methods: Plasma adrenomedullin levels were measured in 17 healthy subjects and 34 cirrhotic patients . Hemodynamic parameters. renal function, and levels of vasoactive sub stances were also assessed. Results: Patients with ascites had increas ed adrenomedullin levels (289 +/- 47 pg/ml) compared with healthy subj ects and patients without ascites (135 +/- 17 and 142 +/- 32 pg/mL, re spectively; P < 0.05). Adrenomedullin levels correlated inversely with arterial pressure, glomerular filtration rate, and renal plasma flow and correlated directly with pulse rate, endothelin levels, and aldost erone and plasma renin activity. In cirrhotic patients, no significant differences in adrenomedullin levels were found between samples obtai ned from hepatic vein, renal vein, pulmonary artery, and femoral arter y. Plasma expansion with albumin suppressed the renin-angiotensin syst em but did not affect adrenomedullin levels. Conclusions: Circulating levels of adrenomedullin are increased in patients with ascites and co rrelate with hemodynamic and renal abnormalities and activation of vas oconstrictor systems. These increased levels seem to result from a gen eralized increase in adrenomedullin production from vascular tissue an d are not suppressed by plasma expansion. Adrenomedullin may participa te in the pathogenesis of arterial vasodilation in cirrhosis.