Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure

Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure
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DOI:
10.1097/00004872-200104000-00014
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发表时间:
2001-04-01
影响因子:
4.9
通讯作者:
Kangawa, K
Kangawa, K
中科院分区:
医学2区
文献类型:
--
作者:
Nishikimi, T;Horio, T;Kangawa, K

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目的人肾上腺髓质素前体被转化为甘氨酸延伸的肾上腺髓质素(AM-Gly),AM-Gly是肾上腺髓质素的一种中间失活形式。随后,AM-Gly转化为成熟肾上腺素调节素(AM-m)的活性形式。本研究的目的是研究(i)性别或年龄是否影响正常受试者血浆和尿液AM-m和AM-Gly水平;(ii)血浆AM-m和AM-Gly的日间变异性(iii)正常受试者、患有原发性高血压(HT)和慢性肾衰竭(CRF)的个体的血浆和尿中的AM-m和AM-Gly水平及其比率;方法采用放射免疫法测定各组大鼠血浆和尿中AM-m、AM-Gly和AM-T的含量(AM-m + AM-Gly)的免疫放射分析法测定正常人(n = 81)、HT(n = 28)和CRF(n = 30)中的AM-m + AM-Gly,我们还测定了疑似肾血管性高血压患者(n = 9)血管造影期间不同部位血浆肾上腺髓质素的分子形式。结果正常人血浆和尿液中两种分子形式肾上腺髓质素的排泄量在性别和年龄上均无差异,正常人血浆肾上腺髓质素的两种分子形式无日间变化。血浆AM-m、AM-Gly和AM-T水平在慢性肾功能衰竭患者中均高于正常人。而尿AM-m、AM-Gly和AM-T排泄量在慢性肾功能不全组较正常组明显减少。尿AM-m:AM-T比值显著高于血浆AM-m:AM-T比值。血浆AM-m和AM-T水平在不同静脉中相似,均显著高于主动脉,而主动脉和静脉间AM-Gly水平无差异。结论正常人、HT和CRF患者血浆和尿液AM-m和AM-Gly的排泄不受年龄和性别的影响;(ii)AM-m与AM-Gly平行增加;(iii)尿液中活性肾上腺髓质素的百分比高于血浆;和(iv)血浆AM-m可能部分在肾脏代谢。(C)2001年利平科特威廉姆斯&威尔金斯。
Objectives 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 adrenomeduliin (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.Methods 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).Results 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 Hi 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.Conclusions 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 lu ng. (C) 2001 Lippincott Williams & Wilkins.