Brain natriuretic peptide as a novel cardiac hormone in humans: Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide

M. Mukoyama, K. Nakao, K. Hosoda, S. I. Suga, Y. Saito, Y. Ogawa, G. Shirakami, M. Jougasaki, K. Obata, H. Yasue, Y. Kambayashi, K. Inouye, H. Imura

Research output: Contribution to journalArticle

1166 Citations (Scopus)

Abstract

Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 ± 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, Δ((CS-Ao))BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [Δ((AIV-Ao))BNP] was comparable to Δ((CS-Ao))BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than α-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of α-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.

Original languageEnglish
Pages (from-to)1402-1412
Number of pages11
JournalJournal of Clinical Investigation
Volume87
Issue number4
DOIs
Publication statusPublished - Jan 1 1991

Fingerprint

Natriuretic Peptides
Brain Natriuretic Peptide
Atrial Natriuretic Factor
Coronary Sinus
Hormones
Heart Failure
Catheterization
Northern Blotting
Radioimmunoassay
Veins
Pharmacokinetics
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Brain natriuretic peptide as a novel cardiac hormone in humans : Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. / Mukoyama, M.; Nakao, K.; Hosoda, K.; Suga, S. I.; Saito, Y.; Ogawa, Y.; Shirakami, G.; Jougasaki, M.; Obata, K.; Yasue, H.; Kambayashi, Y.; Inouye, K.; Imura, H.

In: Journal of Clinical Investigation, Vol. 87, No. 4, 01.01.1991, p. 1402-1412.

Research output: Contribution to journalArticle

Mukoyama, M, Nakao, K, Hosoda, K, Suga, SI, Saito, Y, Ogawa, Y, Shirakami, G, Jougasaki, M, Obata, K, Yasue, H, Kambayashi, Y, Inouye, K & Imura, H 1991, 'Brain natriuretic peptide as a novel cardiac hormone in humans: Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide', Journal of Clinical Investigation, vol. 87, no. 4, pp. 1402-1412. https://doi.org/10.1172/JCI115146
Mukoyama, M. ; Nakao, K. ; Hosoda, K. ; Suga, S. I. ; Saito, Y. ; Ogawa, Y. ; Shirakami, G. ; Jougasaki, M. ; Obata, K. ; Yasue, H. ; Kambayashi, Y. ; Inouye, K. ; Imura, H. / Brain natriuretic peptide as a novel cardiac hormone in humans : Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 4. pp. 1402-1412.
@article{3205b8d3cda24034a394793075eb99e9,
title = "Brain natriuretic peptide as a novel cardiac hormone in humans: Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide",
abstract = "Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 ± 0.07 fmol/ml, which was 16{\%} of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, Δ((CS-Ao))BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [Δ((AIV-Ao))BNP] was comparable to Δ((CS-Ao))BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than α-hANP; this was in part attributed to lower (about 7{\%}) binding affinity of hBNP to clearance receptors than that of α-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.",
author = "M. Mukoyama and K. Nakao and K. Hosoda and Suga, {S. I.} and Y. Saito and Y. Ogawa and G. Shirakami and M. Jougasaki and K. Obata and H. Yasue and Y. Kambayashi and K. Inouye and H. Imura",
year = "1991",
month = "1",
day = "1",
doi = "10.1172/JCI115146",
language = "English",
volume = "87",
pages = "1402--1412",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "4",

}

TY - JOUR

T1 - Brain natriuretic peptide as a novel cardiac hormone in humans

T2 - Evidence for an exquisite dual natriuretic peptide system, atrial natriuretic peptide and brain natriuretic peptide

AU - Mukoyama, M.

AU - Nakao, K.

AU - Hosoda, K.

AU - Suga, S. I.

AU - Saito, Y.

AU - Ogawa, Y.

AU - Shirakami, G.

AU - Jougasaki, M.

AU - Obata, K.

AU - Yasue, H.

AU - Kambayashi, Y.

AU - Inouye, K.

AU - Imura, H.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 ± 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, Δ((CS-Ao))BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [Δ((AIV-Ao))BNP] was comparable to Δ((CS-Ao))BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than α-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of α-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.

AB - Using a specific radioimmunoassay for human brain natriuretic peptide (hBNP) with a monoclonal antibody, we have investigated its synthesis, secretion, and clearance in comparison with those of atrial natriuretic peptide (ANP) in normal subjects and patients with congestive heart failure (CHF). Mean BNP-like immunoreactivity (-LI) levels in normal atrium and ventricle were 250 and 18 pmol/g, respectively. The plasma BNP-LI level in normal subjects was 0.90 ± 0.07 fmol/ml, which was 16% of the ANP-LI level. In contrast, the plasma BNP-LI level markedly increased in patients with CHF in proportion to its severity, and surpassed the ANP-LI level in severe cases. There was a significant step-up of the plasma BNP-LI level in the coronary sinus (CS) compared with that in the aortic root (Ao) and the difference between these BNP-LI levels, Δ((CS-Ao))BNP, also increased with the severity of CHF. In addition, the step-up of the BNP-LI level in the anterior interventricular vein [Δ((AIV-Ao))BNP] was comparable to Δ((CS-Ao))BNP, indicating that BNP is secreted mainly from the ventricle. Predominant BNP synthesis in the ventricle was also confirmed by Northern blot analysis. Catheterization and pharmacokinetic studies revealed that hBNP is cleared from the circulation more slowly than α-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of α-hANP. A predominant molecular form of BNP-LI in the heart and plasma was a 3-kD form corresponding to hBNP. These results indicate that BNP is a novel cardiac hormone secreted predominantly from the ventricle, and that the synthesis, secretion and clearance of BNP differ from those of ANP, suggesting discrete physiological and pathophysiological roles of BNP in a dual natriuretic peptide system.

UR - http://www.scopus.com/inward/record.url?scp=0025729993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025729993&partnerID=8YFLogxK

U2 - 10.1172/JCI115146

DO - 10.1172/JCI115146

M3 - Article

C2 - 1849149

AN - SCOPUS:0025729993

VL - 87

SP - 1402

EP - 1412

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 4

ER -