title: Increased plasma levels of adrenomedullin in patients with heart failure.
abstract: OBJECTIVE
  To investigate the role of adrenomedullin in the pathophysiology of heart failure, we measured plasma levels of adrenomedullin in patients with heart failure.
  
  
  BACKGROUND
  Adrenomedullin is a potent hypotensive peptide newly discovered in pheochromocytoma tissue by monitoring its elevating activity on platelet adenosine 3',5'-cyclic monophosphate (cAMP). A significant level of adrenomedullin has been identified in human plasma. These findings suggest the possibility of adrenomedullin as a 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 i.v. (n = 10) and from normal subjects (n = 27). Plasma adrenomedullin levels were determined by our newly developed radioimmunoassay. Other humoral factor levels measured simultaneously included norepinephrine, atrial natriuretic peptide, brain natriuretic peptide, plasma renin activity, aldosterone and cAMP. Left ventricular ejection fraction was measured by echocardiography. In eight patients with severe heart failure, plasma adrenomedullin levels were measured before and after treatment.
  
  
  RESULTS
  The mean (+/- SD) plasma level of adrenomedullin in control subjects was 2.52 +/- 0.75 pmol/liter. Plasma 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 i.v. (4.78 +/- 1.218 and 8.74 +/- 3.43 pmol/liter, respectively). There was a significant correlation between plasma 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 plasma adrenomedullin levels (r = 0.485, p < 0.001). Plasma 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 plasma level of adrenomedullin are elevated in heart failure and that an increased plasma 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.
authors.affiliation: Division of Hypertension and Nephrology, National Cardiovascular Center, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nishikimi
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Ishimitsu
authors.forename: T
authors.initials: T
authors.lastname: Eto
authors.forename: K
authors.initials: K
authors.lastname: Kangawa
authors.forename: H
authors.initials: H
authors.lastname: Matsuo
authors.forename: T
authors.initials: T
authors.lastname: Omae
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000097:blood; D000959:Antihypertensive Agents / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010455:Peptides / Q000097:blood* / Q000502:physiology; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D009419:Nerve Tissue Proteins; D010455:Peptides; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D012083:Renin; D009638:Norepinephrine