Elevation of two molecular forms of adrenomedullin in plasma and urine in patients with acute myocardial infarction treated with early coronary angioplasty.
Adrenomedullin (AM) has vasodilatory, diuretic and natriuretic actions. Two molecular forms of AM circulate in human plasma: an active, mature form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly). In the present study we investigated the pathophysiological significance of the two molecular forms of AM in plasma and urine in patients with acute myocardial infarction. We serially measured venous and arterial plasma levels and urinary excretion of AM-m, AM-Gly and total AM (Am-T; =AM-m+AM-Gly) over 2 weeks using our recently developed immunoradiometric assay in 26 consecutive patients with acute myocardial infarction and in age-matched normal controls, and studied the relationships between AM levels and clinical parameters. Plasma AM-m, AM-Gly and AM-T levels were increased on admission in patients with acute myocardial infarction compared with age-matched normal controls. Levels of AM-m, AM-Gly and AM-T in plasma reached a peak 24 h after the onset of symptoms. Plasma AM-m, AM-Gly and AM-T levels were significantly correlated with plasma levels of brain natriuretic peptide and pulmonary arterial pressure. Plasma AM-Gly levels in the vein were similar to those in the artery, whereas plasma AM-m levels were significantly lower in the artery than in the vein. Urinary excretion of AM-m, AM-Gly and AM-T was also increased on admission, and reached a peak at 12 h after the onset of symptoms. Urinary excretion of AM-m and AM-Gly was significantly correlated with urinary sodium excretion. The AM-m/AM-T ratio was significantly higher in the urine than in the vein or artery. AM-m levels were significantly correlated with AM-Gly levels in both the urine and plasma; however, there were no significant correlations between plasma and urinary AM levels. The results suggest that levels of both molecular forms of AM are increased in the urine as well as in the plasma in the acute phase of myocardial infarction. Since AM exerts potent cardiovascular and renal effects, increased concentrations of AM in plasma and urine in the acute phase of myocardial infarction may be involved in the defence mechanism against further elevations of peripheral and pulmonary vascular resistance and oliguria in acute myocardial infarction.
Asakawa
H
H
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.
Nishikimi
T
T
Suzuki
T
T
Hara
S
S
Tsubokou
Y
Y
Yagi
H
H
Yabe
A
A
Tsuchiya
N
N
Horinaka
S
S
Kangawa
K
K
Matsuoka
H
H
D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D009320:Atrial Natriuretic Factor / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D015592:Immunoradiometric Assay; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000628:therapy; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010455:Peptides / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012964:Sodium / Q000652:urine
D010455:Peptides; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D012964:Sodium