Increased plasm levels of adrenomedullin in patients with heart failure

Objectives. To investigate the role of adrenomedullin in the pathophysiology of heart failure, we measured plasm levels of adrenomedullin in patients with heart failure. Background. Adrenomedullin is potent hypotensive peptide newly discovered in pheochromocytom tissue by monitoring its elevating activity on platelet adenosine 3′, 5′-cyclic monophosphate (cAMP). significant level of adrenomedullin has been identified in human plasma. These findings suggest the possibility of adrenomedullin as new circulating hormone that participates in the regulation of the cardiovascular system. Methods. Venous blood samples at rest were obtained from patients with heart failure in New York Heart Association functional classes I (n = 15), II (n = 25), III (n = 16) and IV (n = 10) and from normal subjects (n = 27). Plasm adrenomedullin levels were determined by our newly developed radioimmunoassay. Other humoral factor levels measured simultaneously included norepinephrine, atrial natriuretic peptide, brain natriuretic peptide, plasm renin activity, aldosterone and cAMP. Left ventricular ejection fraction was measured by echocardiography. In eight patients with severe heart failure, plasm adrenomedullin levels were measured before and after treatment. Results. The mean (± SD) plasm level of adrenomedullin in control subjects was 2.52 ± 0.75 pmollliter. Plasm levels of adrenomedullin in patients with heart failure were unaffected in those in functional class I (2.85 ± 0.62 pmol/liter) but tended to be increased in those in class II (3.54 ± 0.82 pmol/liter) and were significantly increased in those in classes III and IV (4.78 ± 1.218 and 8.74 ± 3.42 pmollliter, respectively). There was significant correlation between plasm levels of adrenomedullin and norepinephrine (r = 0.618, p < 0.001), atrial natriuretic peptide (r = 0.696, p < 0.001) and brain natriuretic peptide (r = 0.692, p < 0.001). Left ventricular ejection fraction inversely correlated with plasm adrenomedullin levels (r = 0.485, p < 0.001). Plasm adrenomedullin levels significantly decreased after treatment (from 7.40 ± 3.40 to 3.98 ± 1.00 pmol/liter, p < 0.05). Conclusions. These results suggest that plasm levels of adrenomedullin are elevated in heart failure and that an increased plasm volume and an activated sympathetic nervous system in this condition may be related to its synthesis or secretion. Given that adrenomedullin exerts potent cardiovascular effects, increased adrenomedullin may be involved in the defense mechanism against further peripheral vascular resistance elevation in heart failure.