Iervasi G, Clerico A, Pilo A, Vitek F, Berti S, Palmieri C, Ravani M, Sabatino L, Manfredi C, Del Chicca M G, Biagini A, Donato L
Laboratory of Cardiovascular Endocrinology, CNR Institute of Clinical Physiology, Pisa, Italy.
J Clin Endocrinol Metab. 1997 Mar;82(3):884-8. doi: 10.1210/jcem.82.3.3800.
Atrial natiurectic peptide (ANP) is a cardiac hormone with a very short plasma half-life, which plays an important role in a variety of clinical conditions associated with an increase in pressure and/or volume overload on the heart. The MCR of the hormone is considered to represent a stable parameter, reflecting the uptake and degradation rate of ANP by the periphery, only scarcely affected by rapid oscillations of circulating levels. To evaluate the extent to which MCR is affected by rapid and large variations of circulating levels of the hormone, we measured MCR in five patients with different degrees of myocardial function (from normal to severely impaired), in whom changes in ANP levels were induced by atrial and/or ventricular pacing. Cardiac output was simultaneously measured by thermodilution to calculate whole body extraction of ANP. During constant i.v. infusion of [125I]ANP, the hormone MCR was determined both under basal conditions (at tracer equilibration, 20-30 min after the start of infusion) and during atrial and ventricular pacing. Pacing maneuvers, begun 50 min after the start of infusion, induced a marked and rapid increase in endogenous plasma ANP values in all patients (on the average, 3,7-fold compared to basal values; range, 1.8-5.68), whereas corresponding values of [125I]ANP only minimally changed. The MCR of ANP (3.62 +/- 1.06 L/min, mean +/- SD) slightly decreased (by repeated measures ANOVA, P = 0.0458) during atrial and ventricular pacing procedures (3.35 +/- 1.03 and 3.15 +/- 0.74 L/min, respectively), reaching a mean value of 88.7 +/- 9.0% compared to basal. The small decrease in MCR could be almost completely ascribed to hemodynamic factors; indeed, basal cardiac output (5.76 +/- 1.70 L/min) was found, on the average, to be slightly decreased during atrial and ventricular pacing (5.28 +/- 1.46 and 5.16 +/- 1.33 L/min, respectively), and so whole body extraction of the hormone, measured before pacing (50.0 +/- 12%), remains stable throughout the study period (50.4 +/- 10.6% and 49.6 +/- 10% during atrial and ventricular pacing, respectively). Our findings demonstrate that degradative mechanisms involved in ANP clearance are not saturable at least for acute elevations of ANP plasma levels up to 3-5 times the basal level.
心房利钠肽（ANP）是一种血浆半衰期极短的心脏激素，在与心脏压力和/或容量超负荷增加相关的多种临床病症中发挥重要作用。该激素的代谢清除率（MCR）被认为是一个稳定的参数，反映了外周对ANP的摄取和降解速率，几乎不受循环水平快速波动的影响。为了评估MCR受该激素循环水平快速大幅变化影响的程度，我们测量了五名心肌功能程度不同（从正常到严重受损）患者的MCR，这些患者通过心房和/或心室起搏诱导ANP水平发生变化。通过热稀释法同时测量心输出量，以计算全身对ANP的摄取率。在持续静脉输注[125I]ANP期间，在基础条件下（输注开始后20 - 30分钟达到示踪剂平衡时）以及心房和心室起搏期间测定激素MCR。输注开始50分钟后开始的起搏操作在所有患者中均引起内源性血浆ANP值显著快速升高（平均而言，相较于基础值升高3.7倍；范围为1.8 - 5.68），而[125I]ANP的相应值仅发生极小变化。在心房和心室起搏过程中，ANP的MCR（3.62 +/- 1.06 L/分钟，平均值 +/- 标准差）略有下降（通过重复测量方差分析，P = 0.0458）（分别为3.35 +/- 1.03和3.15 +/- 0.74 L/分钟），相较于基础值达到平均值88.7 +/- 9.0%。MCR的小幅下降几乎完全可归因于血流动力学因素；实际上，发现基础心输出量（5.76 +/- 1.70 L/分钟）在心房和心室起搏期间平均略有下降（分别为5.28 +/- 1.46和5.16 +/- 1.33 L/分钟），因此在起搏前测量的激素全身摄取率（50.0 +/- 12%）在整个研究期间保持稳定（心房和心室起搏期间分别为50.4 +/- 10.6%和49.6 +/- 10%）。我们的研究结果表明，至少对于ANP血浆水平急性升高至基础水平的3 - 5倍，参与ANP清除的降解机制不会饱和。
