Nishikimi T, Horio T, Kohmoto Y, Yoshihara F, Nagaya N, Inenaga T, Saito M, Teranishi M, Nakamura M, Ohrui M, Kawano Y, Matsuo H, Ishimitsu T, Takishita S, Matsuoka H, Kangawa K
Research Institute, National Cardiovascular Centre, Osaka, Japan.
J Hypertens. 2001 Apr;19(4):765-73. doi: 10.1097/00004872-200104000-00014.
Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta.
We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9).
There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m: AM-T ratios were significantly higher than plasma AM-m: AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins.
These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.
人肾上腺髓质素前体可转化为甘氨酸延伸型肾上腺髓质素（AM-Gly），这是肾上腺髓质素的一种中间无活性形式。随后，AM-Gly转化为成熟肾上腺髓质素（AM-m）的活性形式。本研究的目的是调查：（i）性别或年龄是否影响正常受试者血浆和尿液中AM-m和AM-Gly的水平；（ii）正常受试者血浆中AM-m和AM-Gly水平的日间变化；（iii）正常受试者、原发性高血压（HT）患者和慢性肾衰竭（CRF）患者血浆和尿液中AM-m、AM-Gly水平及其比值；（iv）不同静脉和主动脉血浆中AM-m与AM-总量（T）的比值。
我们采用最近开发的免疫放射分析法，测量了正常受试者（n = 81）、HT患者（n = 28）和CRF患者（n = 30）血浆中AM-m、AM-Gly和AM-T（AM-m + AM-Gly）的水平以及尿液排泄量。我们还在疑似肾血管性高血压患者（n = 9）的血管造影过程中，测定了取自不同部位的血浆肾上腺髓质素的分子形式。
正常受试者中，两种肾上腺髓质素分子形式的血浆和尿液排泄量在性别或年龄之间没有差异。正常受试者血浆中两种肾上腺髓质素分子形式没有日间变化。与正常受试者相比，HT和CRF患者血浆中AM-m、AM-Gly和AM-T水平升高，而HT和CRF患者尿液中AM-m、AM-Gly和AM-T排泄量减少。尿液中AM-m:AM-T比值显著高于血浆中AM-m:AM-T比值。取自不同静脉的血浆AM-m和AM-T水平相似，且显著高于主动脉的水平，尽管主动脉和静脉之间血浆AM-Gly水平没有差异。
这些结果表明，在正常受试者以及HT和CRF患者中：（i）AM-m和AM-Gly的血浆和尿液排泄不受年龄或性别的影响；（ii）AM-m与AM-Gly同时升高；（iii）尿液中活性肾上腺髓质素的百分比高于血浆；（iv）血浆AM-m可能在肺中部分代谢。
