Itoh H, Nakao K, Sugawara A, Saito Y, Mukoyama M, Morii N, Yamada T, Shiono S, Arai H, Hosoda K
Department of Medicine, Kyoto University School of Medicine, Japan.
J Clin Endocrinol Metab. 1988 Sep;67(3):429-37. doi: 10.1210/jcem-67-3-429.
Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor gamma ANP, that is gamma ANP-(1-25), and alpha ANP [gamma ANP-(99-126)], we studied the secretion of gamma ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected gamma ANP-(1-25)-like immunoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 +/- 62 (+/- SE) pg/mL (174 +/- 21 pmol/L)]; the mean plasma alpha ANP-LI level at the same time in these subjects was 32.8 +/- 4.4 pg/mL (10.7 +/- 1.4 pmol/L). Gel permeation chromatographic analysis of plasma samples from normal subjects and patients with heart disease and chronic renal failure revealed two major components; one was alpha ANP, and the other was the 10K N-terminal gamma ANP fragment (N-peptide) resulting from the removal of alpha ANP (3K) from gamma ANP (13K). In addition, gamma ANP (13K), which possessed both gamma ANP-(1-25)-LI and alpha ANP-LI, and beta ANP, an antiparallel dimer of alpha ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal gamma ANP fragment and alpha ANP (P less than 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal gamma ANP fragment and alpha ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI (17.4 +/- 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 +/- 7.1; P less than 0.01) suggest the slower clearance of the N-terminal gamma ANP fragment than alpha ANP and a role for the kidney in its degradation. Since the molar ratio of plasma gamma ANP-(1-25)-LI to alpha ANP-LI in patients with cirrhosis (20.7 +/- 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal gamma ANP fragment is metabolized by the liver. In patients with heart disease, plasma gamma ANP-(1-25)-LI and alpha ANP-LI levels were higher in those with cardiac decompensation and were positively correlated with right atrial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure, indicating cosecretion of the N-terminal gamma ANP fragment and alpha ANP in response to atrial stretch.(ABSTRACT TRUNCATED AT 400 WORDS)
我们使用放射免疫分析法检测人心房利钠多肽（ANP）前体γ-ANP的N端和C端片段，即γ-ANP-(1-25)和α-ANP [γ-ANP-(99-126)]，研究了正常受试者以及患有心脏病、慢性肾衰竭和肝硬化的患者心脏中γ-ANP衍生肽的分泌情况。我们在17名正常受试者的血浆中检测到大量的γ-ANP-(1-25)样免疫反应性（-LI）[平均值为510±62（±SE）pg/mL（174±21 pmol/L）]；这些受试者同一时间的血浆α-ANP-LI平均水平为32.8±4.4 pg/mL（10.7±1.4 pmol/L）。对正常受试者以及患有心脏病和慢性肾衰竭患者的血浆样本进行凝胶渗透色谱分析，发现有两个主要成分；一个是α-ANP，另一个是从γ-ANP（13K）中去除α-ANP（3K）后产生的10K N端γ-ANP片段（N肽）。此外，在一些患者中还检测到少量的同时具有γ-ANP-(1-25)-LI和α-ANP-LI的γ-ANP（13K）以及α-ANP的反平行二聚体β-ANP。血浆N端γ-ANP片段和α-ANP水平之间存在显著正相关（P<0.01），并且冠状动脉窦血浆中N端γ-ANP片段和α-ANP水平几乎同等程度升高，这表明它们以等摩尔量共同分泌。正常受试者血浆γ-ANP-(1-25)-LI与α-ANP-LI的高摩尔比（17.4±1.4）以及慢性肾衰竭患者中显著更高的比值（36.9±7.1；P<0.01）表明，N端γ-ANP片段的清除比α-ANP慢，且肾脏在其降解过程中起作用。由于肝硬化患者血浆γ-ANP-(1-25)-LI与α-ANP-LI的摩尔比（20.7±2.7）与正常受试者相似，因此N端γ-ANP片段不太可能由肝脏代谢。在心脏病患者中，心脏失代偿患者的血浆γ-ANP-(1-25)-LI和α-ANP-LI水平较高，且与右心房压力、肺动脉压力和肺毛细血管楔压呈正相关，表明N端γ-ANP片段和α-ANP因心房牵张而共同分泌。（摘要截取自400字）
