Pemberton C J, Johnson M L, Yandle T G, Espiner E A
Christchurch Cardioendocrine Research Group, Christchurch School of Medicine, University of Otago, and Christchurch Hospital, Christchurch, New Zealand.
Hypertension. 2000 Sep;36(3):355-9. doi: 10.1161/01.hyp.36.3.355.
Cardiac natriuretic peptides, especially amino terminal pro-Brain Natriuretic Peptide (NT-proBNP), are emerging as powerful circulating markers of cardiac function. However, the in vivo secretion and elimination (t1/2) of these peptides during acute volume overload have not been studied. We present the first report of the secretion and elimination of cardiac natriuretic peptides, based on deconvolution analysis of endogenous ovine plasma levels measured by specific radioimmunoassay. Four normal, conscious sheep underwent rapid right ventricular pacing (225 bpm) for 1 hour to stimulate acute cardiac natriuretic peptide release. Plasma samples and right atrial pressure measurements were taken at regular intervals 30 minutes before, during, and 4 hours after pacing. Baseline right atrial pressure significantly increased (P:=0.02) during the 1 hour of pacing in association with a prompt increase in plasma BNP (P:=0.03), atrial natriuretic peptide (P:=0.01), and NT-proBNP (P:=0.02). Deconvolution analysis showed that the t1/2 of NT-proBNP (69.6+/-10.8 minutes) was 15-fold longer than BNP (4.8+/-1. 0 minutes). Despite sustained increases in atrial pressure, cardiac secretion of natriuretic peptides (particularly atrial natriuretic peptide) fell during the pacing period, suggesting a finite source of peptide for secretion. Size-exclusion high-performance liquid chromatography revealed NT-proBNP to be a single immunoreactive peak, whereas BNP comprised at least 2 immunoreactive forms. These findings, especially the prompt secretion of BNP and the prolonged t1/2 of NT-proBNP, clarify the metabolism of BNP forms and help to explain the diagnostic value of NT-proBNP measurement as a sensitive marker of ventricular function.
心脏利钠肽，尤其是氨基末端前脑利钠肽（NT-proBNP），正逐渐成为心脏功能强大的循环标志物。然而，急性容量超负荷期间这些肽的体内分泌和消除（半衰期）尚未得到研究。我们基于通过特异性放射免疫测定法测量的内源性绵羊血浆水平的反卷积分析，首次报告了心脏利钠肽的分泌和消除情况。对四只正常、清醒的绵羊进行快速右心室起搏（225次/分钟）1小时，以刺激急性心脏利钠肽释放。在起搏前30分钟、起搏期间和起搏后4小时定期采集血浆样本并测量右心房压力。在起搏的1小时内，基线右心房压力显著升高（P = 0.02），同时血浆脑钠肽（BNP，P = 0.03）、心房利钠肽（P = 0.01）和NT-proBNP（P = 0.02）迅速增加。反卷积分析显示，NT-proBNP的半衰期（69.6±10.8分钟）比BNP（4.8±1.0分钟）长15倍。尽管心房压力持续升高，但在起搏期间利钠肽（尤其是心房利钠肽）的心脏分泌下降，提示肽的分泌来源有限。尺寸排阻高效液相色谱显示NT-proBNP为单一免疫反应峰，而BNP至少包含2种免疫反应形式。这些发现，尤其是BNP的迅速分泌和NT-proBNP的延长半衰期，阐明了BNP形式的代谢，并有助于解释NT-proBNP测量作为心室功能敏感标志物的诊断价值。
