title: Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.
abstract: Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.
authors.affiliation: Division of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kakishita
authors.forename: T
authors.initials: T
authors.lastname: Nishikimi
authors.forename: Y
authors.initials: Y
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: S
authors.initials: S
authors.lastname: Kyotani
authors.forename: N
authors.initials: N
authors.lastname: Nagaya
authors.forename: K
authors.initials: K
authors.lastname: Fukushima
authors.forename: N
authors.initials: N
authors.lastname: Nakanishi
authors.forename: S
authors.initials: S
authors.lastname: Takishita
authors.forename: A
authors.initials: A
authors.lastname: Miyata
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: Kunieda
mesh_terms: D000280:Administration, Inhalation; D053607:Adrenomedullin; D000368:Aged; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood; D006328:Cardiac Catheterization; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage; D010455:Peptides / Q000097:blood*; D011863:Radioimmunoassay; D012044:Regression Analysis; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor