Naomi S, Umeda T, Iwaoka T, Miura F, Sasaki M, Nakayama M, Kitamoto Y, Sato T
Third Department of Internal Medicine, Kumamoto University Medical School, Japan.
Nihon Naibunpi Gakkai Zasshi. 1989 Mar 20;65(3):152-60. doi: 10.1507/endocrine1927.65.3_152.
To clarify the molecular nature and dynamics of circulating alpha human atrial natriuretic polypeptide (alpha hANP) in chronic renal disease, the plasma concentrations of alpha hANP were determined by radioimmunoassays using two distinct monoclonal antibodies (MoAbs). One MoAb (10B1) recognized N-terminus of alpha hANP, while the other (C351) recognized the ring structure. The preliminary studies revealed a close correlation (r = 0.97, p less than 0.0001) between plasma alpha hANP measured with 10B1 and C351 MoAbs, supporting the theory that the main circulating form is alpha hANP(1-28). Therefore, the more sensitive radioimmunoassay using MoAb (C351) was used in the present studies. The plasma alpha hANP was 3.8 +/- 1.7 (mean +/- SD) in healthy subjects, 2.7 +/- 1.4 fmol/ml in patients with chronic glomerulonephritis without renal failure, 16.2 +/- 16.8 fmol/ml in patients with chronic renal failure, and 24.3 +/- 10.5 fmol/ml in patients under maintenance hemodialysis. Thus, the elevation of plasma alpha hANP was related to the stages of renal damage. Although the plasma alpha hANP in 18 patients under maintenance hemodialysis declined significantly (p less than 0.01) after hemodialysis, their levels (17.9 +/- 9.0 fmol/ml) after hemodialysis were still higher than those in healthy subjects. On the other hand, a positive correlation (r = 0.65, p less than 0.05) between alpha hANP and creatinine in blood was found only in the group of chronic renal failure before maintenance hemodialysis. These results suggest that an impaired metabolism of alpha hANP in the kidney might play an important role in the elevation of plasma alpha hANP as well as the stimulation of alpha hANP secretion caused by the expansion of extracellular fluid.
为阐明慢性肾病中循环α人心房利钠多肽(α hANP)的分子性质和动态变化,使用两种不同的单克隆抗体(MoAbs)通过放射免疫分析法测定血浆α hANP浓度。一种MoAb(10B1)识别α hANP的N端,而另一种(C351)识别环结构。初步研究显示,用10B1和C351 MoAbs测得的血浆α hANP之间存在密切相关性(r = 0.97,p < 0.0001),支持主要循环形式为α hANP(1 - 28)的理论。因此,本研究采用了更灵敏的使用MoAb(C351)的放射免疫分析法。健康受试者的血浆α hANP为3.8 ± 1.7(平均值±标准差),无肾衰竭的慢性肾小球肾炎患者为2.7 ± 1.4 fmol/ml,慢性肾衰竭患者为16.2 ± 16.8 fmol/ml,维持性血液透析患者为24.3 ± 10.5 fmol/ml。因此,血浆α hANP的升高与肾损伤阶段相关。尽管18例维持性血液透析患者的血浆α hANP在血液透析后显著下降(p < 0.01),但透析后的水平(17.9 ± 9.0 fmol/ml)仍高于健康受试者。另一方面,仅在维持性血液透析前的慢性肾衰竭组中发现α hANP与血液中肌酐呈正相关(r = 0.65,p < 0.05)。这些结果表明,肾脏中α hANP代谢受损可能在血浆α hANP升高以及细胞外液扩张引起的α hANP分泌刺激中起重要作用。