Author + information
- Received January 27, 1995
- Revision received June 15, 1995
- Accepted June 21, 1995
- Published online November 15, 1995.
- Toshio Nishikimi, MDa,*,
- Yoshihiko Saito, MDa,
- Kazuo Kitamura, MDa,*,
- Toshihiko Ishimitsu, MDa,
- Tanenao Eto, MDa,*,
- Kenji Kangawa, PhDa,
- Hisayuki Matsuo, PhDa,
- Teruo Omae, MDa and
- Hiroaki Matsuoka, MDa
- ↵*Address for correspondence:Dr. Toshio Nishikimi, Division of Hypertension and Nephrology, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565, Japan.
Objectives. 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 IV (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 pmollliter. 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 IV (4.78 ± 1.218 and 8.74 ± 3.42 pmollliter, 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 levels 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.
This work was supported in part by Special Coordination Funds for Promoting Science and Technology (Encouragement System of COE) from the Science and Technology Agency of Japan, Japanese Ministry of Health and Welfare, Human Science Foundation of Japan and Ueda Memorial Heart Foundation, Tokyo, Japan.
- Received January 27, 1995.
- Revision received June 15, 1995.
- Accepted June 21, 1995.
- American College of Cardiology