Drexler H, Hänze J, Finckh M, Lu W, Just H, Lang R E
Medizinische Klinik III, University of Freiburg, FRG.
Circulation. 1989 Mar;79(3):620-33. doi: 10.1161/01.cir.79.3.620.
This study examined the relation between synthesis, atrial storage, and plasma levels of atrial natriuretic peptide (ANP), and it examined plasma ANP levels and hemodynamic output in response to volume expansion in a rat model of myocardial infarction and failure. Arterial ANP concentrations did not correlate linearly with infarct size, but they did show an abrupt increase when infarct size exceeded 30% of the left ventricle, similar to the abrupt increase of left ventricular end-diastolic pressure with infarct size greater than 30%. Consequently, a close relation was found between plasma ANP levels and left ventricular end-diastolic pressure (n = 23, r = 0.89, p less than 0.001). Atrial ANP content per gram of tissue but not ANP content per pair of atria was reduced in rats with large infarcts (greater than 40%, p less than 0.05 vs. control animals). ANP mRNA level per pair of atria (related to total atrial RNA), determined by liquid hybridization (controlled by northern blot analysis), was increased by 38% in infarcted rats (p less than 0.05 vs. controls), but the ratio of atrial ANP mRNA relative to atrial beta-actin mRNA levels was not increased. Right and left ventricular ANP mRNA level increased by 90% and 380%, respectively, far exceeding the concomitant increase in beta-actin mRNA (+26% in the left ventricle). Plasma ANP increased with volume loading in controls and rats with moderate infarcts but not in rats with large infarcts despite a similar increase in right atrial pressure (compared with control animals); thus, the relation of delta ANP/delta right atrial pressure exerted by volume loading decreased in rats with large infarcts. Similarly, the response of cardiac output and renal blood flow (determined by radioactive microspheres) to volume loading was attenuated in rats with large infarcts. Thus, in this model of chronic cardiac failure, the activation of the ANP system is closely coupled with the increase in intracardiac pressures without correlating linearly to the extent of myocardial loss. Second, in severe cardiac failure, additional stimulation such as volume loading may elicit only an attenuated ANP secretion response, for example, due to saturation of the ANP receptor sensing system or to a limited transformation rate of pro-ANP. Third, the increase in atrial ANP synthesis and the increase in atrial ANP gene expression seems limited; however, substantial specific ANP gene expression occurs in the ventricles, which, in turn, may contribute to increased plasma ANP levels in chronic heart failure.
本研究检测了心房利钠肽（ANP）的合成、心房储存与血浆水平之间的关系，并检测了心肌梗死和衰竭大鼠模型中血浆ANP水平及容量扩张后的血流动力学输出。动脉ANP浓度与梗死面积并非呈线性相关，但当梗死面积超过左心室的30%时，ANP浓度会突然升高，这与梗死面积大于30%时左心室舒张末期压力的突然升高相似。因此，发现血浆ANP水平与左心室舒张末期压力之间存在密切关系（n = 23，r = 0.89，p < 0.001）。梗死面积大的大鼠（大于40%，与对照动物相比p < 0.05）每克组织的心房ANP含量降低，但每对心房的ANP含量未降低。通过液体杂交（由Northern印迹分析控制）测定的每对心房的ANP mRNA水平（与总心房RNA相关）在梗死大鼠中增加了38%（与对照相比p < 0.05），但心房ANP mRNA相对于心房β-肌动蛋白mRNA水平的比值未增加。右心室和左心室的ANP mRNA水平分别增加了90%和380%，远远超过了β-肌动蛋白mRNA的相应增加（左心室增加26%）。在对照动物和梗死面积中等的大鼠中，血浆ANP随容量负荷增加，但在梗死面积大的大鼠中不增加，尽管右心房压力有类似增加（与对照动物相比）；因此，容量负荷引起的ΔANP/Δ右心房压力的关系在梗死面积大的大鼠中降低。同样，梗死面积大的大鼠中，心输出量和肾血流量（通过放射性微球测定）对容量负荷的反应减弱。因此，在这种慢性心力衰竭模型中，ANP系统的激活与心内压力的增加密切相关，但与心肌损失程度并非呈线性相关。其次，在严重心力衰竭中，额外的刺激如容量负荷可能仅引起减弱的ANP分泌反应，例如，由于ANP受体传感系统饱和或前ANP转化率有限。第三，心房ANP合成的增加和心房ANP基因表达的增加似乎有限；然而，心室中出现大量特异性ANP基因表达，这反过来可能导致慢性心力衰竭中血浆ANP水平升高。
