γ-Atrial natriuretic polypeptide (γANP)-Derived peptides in human plasma: Cosecretion of n-terminal γANP fragment and αANP

Hiroshi Itoh, Kazuwa Nakao, Akira Sugawara, Yoshihiko Saito, Masashi Mukoyama, Narito Morii, Takayuki Yamada, Shozo Shiono, Hiroshi Arai, Kiminqri Hosoda, Hiroo Imura

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Abstract

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor γANP, that is γANP-(1–25), and αANP[γANP-(99–126)], we studied the secretion of γANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected γANP-(1–25)-like im-munoreactivity (-LI) in plasma from normal subjects (n = 17) in considerable amounts [mean, 510 ± 62 (±SE) pg/mL (174 ± 21 pmol/L)]; the mean plasma αANP-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 aANP, and the other was the 10K N-terminal γANP fragment (N-peptide) resulting from the removal of γANP (3K) from γANP (13K). In addition, γANP (13K), which possessed both γANP-(1–25)-LI and αANP-LI, and βANP, an antiparallel dimer of αANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal γANP fragment and αANP (P < 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal γANP fragment and αANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma γANP-(1–25)-LI to αANP-LI (17.4 ± 1.4) in normal subjects and the significantly higher ratio in patients with chronic renal failure (36.9 ± 7.1; P < 0.01) suggest the slower clearance of the N-terminal γANP fragment than αANP and a role for the kidney in its degradation. Since the molar ratio of plasma γANP-(1–25)-LI to αANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal γANP fragment is metabolized by the liver. In patients with heart disease, plasma γANP-(1–25)-LI and αANP-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 γANP fragment and αANP in response to atrial stretch. The molar ratio of plasma γANP-U-25)-LI to αANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P γ 0.05), suggesting an alteration in the secretion and/or metabolism of γANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal γANP fragment and αANP would serve as a clinical indicator of cardiac or renal function and posssess potential usefulness for detecting abnormalities in the structure, secretion, and metabolic clearance of ANP.

Original languageEnglish
Pages (from-to)429-437
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume67
Issue number3
DOIs
Publication statusPublished - 1988 Sep

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Itoh, H., Nakao, K., Sugawara, A., Saito, Y., Mukoyama, M., Morii, N., Yamada, T., Shiono, S., Arai, H., Hosoda, K., & Imura, H. (1988). γ-Atrial natriuretic polypeptide (γANP)-Derived peptides in human plasma: Cosecretion of n-terminal γANP fragment and αANP. Journal of Clinical Endocrinology and Metabolism, 67(3), 429-437. https://doi.org/10.1210/jcem-67-3-429