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
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
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DOI：
10.1172/jci115146
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发表时间：
1991-04-01
影响因子：
15.9
通讯作者：
IMURA, H
中科院分区：
文献类型：
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作者：
MUKOYAMA, M;NAKAO, K;IMURA, H
我们使用一种带有单克隆抗体的人脑钠肽（hBNP）特异性放射免疫测定法，研究了其与正常受试者和充血性心力衰竭（CHF）患者心房钠肽（ANP）的合成、分泌和清除情况。正常心房和心室的平均bnp样免疫反应性（-LI）水平分别为250和18 pmol/g。正常人血浆BNP-LI水平为0.90±0.07 fmol/ml，为ANP-LI水平的16%。相比之下，CHF患者血浆BNP-LI水平与严重程度成比例显著升高，严重者超过ANP-LI水平。与主动脉根（Ao）相比，冠状窦（CS）血浆BNP- li水平明显升高，两者之间的差异，DELTA(CS-Ao)BNP也随着CHF的严重程度而增加。此外，前室间静脉[DELTA(AIV-Ao)BNP]中BNP- li水平的升高与DELTA(CS-Ao)BNP相当，表明BNP主要由心室分泌。Northern blot分析也证实了脑室中占优势的BNP合成。导管插管和药代动力学研究表明，hBNP从循环中清除的速度比α - hanp慢；这在一定程度上是由于hBNP与清除受体的结合亲和力低于α - hanp（约7%）。BNP-LI在心脏和血浆中的主要分子形式是与hBNP对应的3-kD形式。这些结果表明，BNP是一种主要由心室分泌的新型心脏激素，BNP的合成、分泌和清除与ANP不同，提示BNP在双利钠肽系统中具有离散的生理和病理生理作用。
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, DELTA(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 [DELTA(AIV-Ao)BNP] was comparable to DELTA(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 alpha-hANP; this was in part attributed to lower (about 7%) binding affinity of hBNP to clearance receptors than that of alpha-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.