Mukoyama M, Nakao K, Hosoda K, Suga S, Saito Y, Ogawa Y, Shirakami G, Jougasaki M, Obata K, Yasue H
Department of Medicine, Kyoto University School of Medicine, Japan.
J Clin Invest. 1991 Apr;87(4):1402-12. doi: 10.1172/JCI115146.
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.
我们使用一种针对人脑钠肽（hBNP）的特异性放射免疫分析法，该方法采用单克隆抗体，研究了正常受试者和充血性心力衰竭（CHF）患者中hBNP与心房钠尿肽（ANP）相比的合成、分泌及清除情况。正常心房和心室中脑钠肽样免疫反应性（-LI）水平分别为250和18 pmol/g。正常受试者血浆脑钠肽-LI水平为0.90±0.07 fmol/ml，为心房钠尿肽-LI水平的16%。相比之下，CHF患者血浆脑钠肽-LI水平随病情严重程度显著升高，在严重病例中超过了心房钠尿肽-LI水平。与主动脉根部（Ao）相比，冠状窦（CS）血浆脑钠肽-LI水平显著升高，且这些脑钠肽-LI水平的差值[δ（CS-Ao）BNP]也随CHF严重程度增加。此外，前室间静脉脑钠肽-LI水平的升高[δ（AIV-Ao）BNP]与δ（CS-Ao）BNP相当，表明脑钠肽主要从心室分泌。Northern印迹分析也证实了心室中脑钠肽的主要合成。导管插入术和药代动力学研究表明，hBNP从循环中清除的速度比α-hANP慢；这部分归因于hBNP与清除受体的结合亲和力比α-hANP低（约7%）。心脏和血浆中脑钠肽-LI的主要分子形式是对应于hBNP的3-kD形式。这些结果表明，脑钠肽是一种主要从心室分泌的新型心脏激素，其合成、分泌和清除与心房钠尿肽不同，提示在双钠尿肽系统中脑钠肽具有独特的生理和病理生理作用。
