Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53±10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9±2.5 and 10.6±2.1 pmol/l respectively; AM-Gly, 14.0±2.1 and 9.8±1.9 pmol/l respectively; AM-m, 1.9±0.6 and 1.1±0.3 pmol/l respectively; each P < 0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1±2.7 and 14.0±2.4 pmol/l respectively; AM-m, 2.0±0.6 and 0.7±0.2 pmol/l respectively; each P < 0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1±2.3 and 13.5±2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r = 0.67; AM-Gly, r = 0.63; AM-m, r = 0.59; each P < 0.001) and total pulmonary vascular resistance (AM-T, r = 0.77; AM-Gly, r = 0.70; AM-m, r = 0.75; each P < 0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.
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Research Article|
December 13 2000
The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension
Toshio NISHIKIMI;
*Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
†Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
Correspondence: Dr Toshio Nishikimi, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan (e-mail [email protected]).
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Seiki NAGATA;
Seiki NAGATA
*Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Tatsuya SASAKI;
Tatsuya SASAKI
*Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Fumiki YOSHIHARA;
Fumiki YOSHIHARA
‡Research Institute, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Noritoshi NAGAYA;
Noritoshi NAGAYA
*Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Takeshi HORIO;
Takeshi HORIO
*Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Hisayuki MATSUO;
Hisayuki MATSUO
‡Research Institute, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Hiroaki MATSUOKA;
Hiroaki MATSUOKA
†Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan
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Kenji KANGAWA
Kenji KANGAWA
‡Research Institute, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Publisher: Portland Press Ltd
Received:
May 04 2000
Revision Received:
July 13 2000
Accepted:
September 26 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 100 (1): 61–66.
Article history
Received:
May 04 2000
Revision Received:
July 13 2000
Accepted:
September 26 2000
Citation
Toshio NISHIKIMI, Seiki NAGATA, Tatsuya SASAKI, Fumiki YOSHIHARA, Noritoshi NAGAYA, Takeshi HORIO, Hisayuki MATSUO, Hiroaki MATSUOKA, Kenji KANGAWA; The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension. Clin Sci (Lond) 1 January 2001; 100 (1): 61–66. doi: https://doi.org/10.1042/cs1000061
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