Increased adrenomedullin levels in cirrhosis:: Relationship with hemodynamic abnormalities and vasoconstrictor systems

Background & Aims: Arterial vasodilation in cirrhosis may be related to increased circulating levels of vasodilators. This study was designed to assess the circulating levels of adrenomedullin, a recently described 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 substances were also assessed. Results: Patients with ascites had increased adrenomedullin levels (289 +/- 47 pg/ml) compared with healthy subjects and patients without ascites (135 +/- 17 and 142 +/- 32 pg/mL, respectively; 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 aldosterone and plasma renin activity. In cirrhotic patients, no significant differences in adrenomedullin levels were found between samples obtained from hepatic vein, renal vein, pulmonary artery, and femoral artery. Plasma expansion with albumin suppressed the renin-angiotensin system but did not affect adrenomedullin levels. Conclusions: Circulating levels of adrenomedullin are increased in patients with ascites and correlate with hemodynamic and renal abnormalities and activation of vasoconstrictor systems. These increased levels seem to result from a generalized increase in adrenomedullin production from vascular tissue and are not suppressed by plasma expansion. Adrenomedullin may participate in the pathogenesis of arterial vasodilation in cirrhosis.