This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by ITOH, H. Articles by IMURA, H. Search for Related Content PubMed PubMed Citation Articles by ITOH, H. Articles by IMURA, H.

-Atrial Natriuretic Polypeptide (ANP)-Derived Peptides in Human Plasma: Cosecretion of N-Terminal ANP Fragment and ANP^*

Second Division, Department of Medicine, Kyoto University School of Medicine (H.I., K.N., A.S., Y.S., M.M., N.M., T. Y., S.S., H.A., K.H., H.I.) Kyoto 606, Japan
The Radioisotope Research Center, Kyoto University (K.N.) Kyoto 606, Japan

Address all correspondence and requests for reprints to: Dr. Kazuwa Nakao, Second Division, Department of Medicine, Kyoto University School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan 606.

Using RIAs for the N- and C-terminal fragments of the human atrial natriuretic polypeptide (ANP) precursor ANP, that is ANP-(1–25), and ANP[ANP-(99–126)], we studied the secretion of ANP-derived peptides from the heart in normal subjects and patients with heart disease, chronic renal failure, and cirrhosis. We detected ANP-(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 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 aANP, and the other was the 10K N-terminal ANP fragment (N-peptide) resulting from the removal of ANP (3K) from ANP (13K). In addition, ANP (13K), which possessed both ANP-(1–25)-LI and ANP-LI, and βANP, an antiparallel dimer of ANP, were detected in some patients as minor components. A significant positive correlation between plasma levels of the N-terminal ANP fragment and ANP (P < 0.01) and almost equal step-ups in the coronary sinus plasma levels of the N-terminal ANP fragment and ANP suggest that they are cosecreted in equimolar amounts. The high molar ratio of plasma ANP-(1–25)-LI to 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 < 0.01) suggest the slower clearance of the N-terminal ANP fragment than ANP and a role for the kidney in its degradation. Since the molar ratio of plasma ANP-(1–25)-LI to ANP-LI in patients with cirrhosis (20.7 ± 2.7) was similar to that in normal subjects, it is unlikely that the N-terminal ANP fragment is metabolized by the liver. In patients with heart disease, plasma ANP-(1–25)-LI and 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 ANP fragment and ANP in response to atrial stretch. The molar ratio of plasma ANP-U-25)-LI to ANP-LI in patients with severe congestive heart failure (8.0 ± 1.2) was significantly lower than that in normal subjects (P 0.05), suggesting an alteration in the secretion and/or metabolism of ANP-derived peptides in these patients. These results indicate that the simultaneous determination of the plasma levels of the N-terminal ANP fragment and ANP 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.

^* This work was supported in part by research grants from the Japanese Ministry of Education, Science, and Culture; the Japanese Ministry of Health and Welfare "Disorders of Adrenal Hormone" Research Committee, Japan, 1987; Life Science Research Project of Institute of Physical and Chemical Research (RIKEN); Japan Tobacco, Inc.; Yamanouchi Foundation for Research on Metabolic Disorders; and research grants for cardiovascular diseases (60A-3 and 62A'-1) from the Japanese Ministry of Health and Welfare.

Received December 29, 1987.

This article has been cited by other articles:

				J. A. Smith, D. Bruusgaard, E. Bodd, and C. Hall Relations between medical history, clinical findings and plasma N-terminal proatrial natriuretic peptide in patients in primary health care Eur J Heart Fail, June 1, 2001; 3(3): 307 - 313. [Abstract] [Full Text] [PDF]

				G. A Sagnella Practical implications of current natriuretic peptide research Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 304 - 315. [PDF]

				C. J. Pemberton, M. L. Johnson, T. G. Yandle, and E. A. Espiner Deconvolution Analysis of Cardiac Natriuretic Peptides During Acute Volume Overload Hypertension, September 1, 2000; 36(3): 355 - 359. [Abstract] [Full Text] [PDF]

				J.A.M Wijbenga, A.H.M.M Balk, F Boomsma, A.J Man in 't Veld, and C Hall Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice Eur. Heart J., October 1, 1999; 20(19): 1424 - 1428. [Abstract] [PDF]

				C. J. Pemberton, T. G. Yandle, M. T. Rademaker, C. J. Charles, G. D. Aitken, and E. A. Espiner Amino-terminal proBNP in ovine plasma: evidence for enhanced secretion in response to cardiac overload Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1200 - H1208. [Abstract] [Full Text] [PDF]

				Y. Numata, K. Dohi, A. Furukawa, S. Kikuoka, H. Asada, T. Fukunaga, Y. Taniguchi, K. Sasakura, T. Tsuji, K. Inouye, et al. Immunoradiometric assay for the N-terminal fragment of proatrial natriuretic peptidein human plasma Clin. Chem., May 1, 1998; 44(5): 1008 - 1013. [Abstract] [Full Text] [PDF]

				J. W. Slot, G. Garruti, S. Martin, V. Oorschot, G. Posthuma, E. W. Kraegen, R. Laybutt, G. Thibault, and D. E. James Glucose Transporter (GLUT-4) Is Targeted to Secretory Granules in Rat Atrial Cardiomyocytes J. Cell Biol., June 16, 1997; 137(6): 1243 - 1254. [Abstract] [Full Text] [PDF]

				H. Leskinen, O. Vuolteenaho, M. Toth, and H. Ruskoaho Atrial Natriuretic Peptide (ANP) Inhibits Its Own Secretion via ANPA Receptors: Altered Effect in Experimental Hypertension Endocrinology, May 1, 1997; 138(5): 1893 - 1902. [Abstract] [Full Text] [PDF]

				H. Leskinen, O. Vuolteenaho, and H. Ruskoaho Combined Inhibition of Endothelin and Angiotensin II Receptors Blocks Volume Load–Induced Cardiac Hormone Release Circ. Res., January 1, 1997; 80(1): 114 - 123. [Abstract] [Full Text]

				H. Vierimaa, M. Hirvinen, V. Tervonen, O. Arjamaa, H. Ruskoaho, and O. Vuolteenaho Pronatriuretic peptide is a sensitive marker of the endocrine function of teleost heart Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E843 - E850. [Abstract] [Full Text] [PDF]

				K. Makikallio, O. Vuolteenaho, P. Jouppila, and J. Rasanen Ultrasonographic and Biochemical Markers of Human Fetal Cardiac Dysfunction in Placental Insufficiency Circulation, April 30, 2002; 105(17): 2058 - 2063. [Abstract] [Full Text] [PDF]