Kakishita M, Nishikimi T, Okano Y, Satoh T, Kyotani S, Nagaya N, Fukushima K, Nakanishi N, Takishita S, Miyata A, Kangawa K, Matsuo H, Kunieda T
Division of Medicine, National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565, Japan.
Clin Sci (Lond). 1999 Jan;96(1):33-9.
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.
肾上腺髓质素是一种强效降压肽，可降低血压和肺血管阻力，并增加肺血流量。肾上腺髓质素及其受体的信使核糖核酸在肺中高度表达，提示肾上腺髓质素在肺循环中具有调节作用。为了研究肾上腺髓质素在肺动脉高压患者中的临床意义，我们研究了肾上腺髓质素血浆水平与肺血流动力学之间的关系。在心脏导管插入术期间采集静脉、动脉和肺动脉血样，并通过特异性放射免疫测定法测量33例连续的重度肺动脉高压患者（12例原发性肺动脉高压，21例慢性血栓栓塞性肺动脉高压；年龄49±16岁，平均肺动脉压50±15mmHg）的肾上腺髓质素血浆水平。此外，在急性吸入一氧化氮前后测量肾上腺髓质素血浆水平。还评估了10.3±4.3个月随访期内血浆肾上腺髓质素的变化（n = 5）。62名健康受试者作为对照组。在对照组的肘前静脉中测量肾上腺髓质素。肺动脉高压患者的肾上腺髓质素血浆水平显著高于对照组（10.1±8.7对4.9±1.1pmol/l，P<0.01）。以自然对数表示的肾上腺髓质素血浆水平与平均右心房压（r = 0.71，P<0.01）、每搏量（r = -0.63，P<0.01）、总肺阻力（r = 0.60，P<0.01）、平均肺动脉压（r = 0.37，P<*0.05）以及血浆心钠素的自然对数（r = 0.63，P<0.01）显著相关。吸入一氧化氮后，肾上腺髓质素血浆水平无显著变化，但在长期随访期内与总肺阻力升高相关显著增加。这些结果表明，肾上腺髓质素血浆水平与肺动脉高压程度成比例增加。
