Nishikimi T, Nagata S, Sasaki T, Yoshihara F, Nagaya N, Horio T, Matsuo H, Matsuoka H, Kangawa K
Department of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan.
Clin Sci (Lond). 2001 Jan;100(1):61-6.
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.
肾上腺髓质素（AM）是一种新型降压肽，它优先扩张肺血管而非体循环血管。这提示AM可能是一种参与肺循环调节的循环激素。最近一项研究显示，两种分子形式的AM，即成熟的活性形式AM（AM-m）和中间的无活性甘氨酸延伸形式AM（AM-Gly），在人体血浆中循环。在本研究中，我们调查了二尖瓣狭窄患者肺循环中两种分子形式AM的产生和清除部位及其病理生理意义。我们使用最近开发的特异性免疫放射分析法测量了28例连续二尖瓣狭窄患者（20例女性和8例男性；年龄53±10岁）从股静脉、肺动脉、左心房和主动脉采集的血样中AM-m和总AM（AM-T；AM-m + AM-Gly）的血浆水平，并由此计算出血浆AM-Gly水平。二尖瓣狭窄患者的AM-T、AM-Gly和AM-m静脉浓度显著高于年龄匹配的正常对照组（AM-T分别为15.9±2.5和10.6±2.1 pmol/L；AM-Gly分别为14.0±2.1和9.8±1.9 pmol/L；AM-m分别为1.9±0.6和1.1±0.3 pmol/L；每组P<0.001）。肺动脉和左心房之间AM-m和AM-T的浓度显著降低（AM-T分别为16.1±2.7和14.0±2.4 pmol/L；AM-m分别为2.0±0.6和0.7±0.2 pmol/L；每组P<0.001）；然而，肺动脉和左心房之间的血浆AM-Gly水平没有差异（分别为14.1±2.3和13.5±2.3 pmol/L）。AM-m、AM-Gly和AM-T的静脉浓度与平均肺动脉压（AM-T，r = 0.67；AM-Gly，r = 0.63；AM-m，r = 0.59；每组P<0.001）和总肺血管阻力（AM-T，r = 0.77；AM-Gly，r = 0.70；AM-m，r = 0.75；每组P<0.001）呈现相似的相关性。这些结果表明，AM-m的血浆浓度与AM-Gly和AM-T的血浆浓度平行升高，并且血浆中AM-m清除的主要部位是肺；肺中摄取的AM-m可能有助于减轻二尖瓣狭窄所致继发性肺动脉高压中肺动脉阻力的增加。
