-transparent.png){kind=logo}
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.
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
May 1996,
American heart journal,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
January 1998,
Polskie Archiwum Medycyny Wewnetrznej,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
August 2000,
Nephron,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
January 1996,
The Journal of clinical endocrinology and metabolism,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
August 1999,
Clinical nephrology,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
January 2000,
Dermatology (Basel, Switzerland),
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
January 1999,
Clinical science (London, England : 1979),
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
February 2000,
Kidney international,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
January 2013,
PloS one,
T Nishikimi, and
Y Saito, and
K Kitamura, and
T Ishimitsu, and
T Eto, and
K Kangawa, and
H Matsuo, and
T Omae, and
H Matsuoka
February 2016,
Peptides,
