Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1.
Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1.
复制标题
CHF 血浆内皮素 1 升高的机制：充血增加肺部内皮素 1 的合成和分泌。
DOI：
10.1016/j.cardiores.2004.03.016
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发表时间：
2004
影响因子：
10.8
通讯作者：
H. Attramadal
中科院分区：
文献类型：
--
作者：
T. von Lueder;H. Kjekshus;T. Edvardsen;E. Øie;S. Urheim;L. Vinge;Muhammed Shakil Ahmed;O. Smiseth;H. Attramadal
目的：肺循环可能导致充血性心力衰竭（CHF）血浆内皮素-1（ET-1）水平升高。本研究的目的是确定 CHF 中肺循环 ET-1 分泌增加的机制。方法：对幼猪进行假手术（n=9）或快速心脏起搏诱发 CHF（215-240 bpm，n=15）。结果：三周的快速起搏导致左心室显着扩张，心脏充盈压增加，收缩力降低（CHF）。 猪）。与假猪相比，CHF 猪的动脉血浆 ET-1 水平增加了 4 倍（P<0.001）。单次浓注多指示剂稀释实验表明，CHF 中 ET-1 的肺部合成和释放增加，而血浆 ET-1 的肺部清除率保持不变，尽管血浆 ET-1 的肺部提取分数显着减少。与对照猪下叶段(1.1±0.1,P<0.02)和CHF猪上叶段(1.1±0.1,P<0.005)相比,CHF猪下叶段肺ECE-1同工酶活性(pmol·min−1·mg Protein−1)选择性升高(2.0±0.3),且与湿/干重显着相关 肺组织样本的比率（R=0.75，P<0.001），即肺充血的标志。此外，充血的肺叶段中的肺泡巨噬细胞被确定为 ET-1 合成和释放增加的可能部位。结论：在快速起搏诱发的 CHF 中，肺充血揭示的复杂心肺相互作用，由于肺 ECE-1 活性增强，导致肺产生和分泌 ET-1 增加。 CHF 发展过程中肺部分泌的 ET-1 是体循环中血浆 ET-1 水平升高的重要因素。
Objective:The pulmonary circulation may contribute to elevated plasma levels of endothelin-1 (ET-1) in congestive heart failure (CHF). The aims of the present study were to determine the mechanisms of increased secretion of ET-1 from the pulmonary circulation in CHF.Methods:Juvenile pigs were subjected to sham operation (n=9) or rapid cardiac pacing-induced CHF (215–240 bpm,n=15).Results:Three weeks of rapid pacing led to significant left ventricular dilatation, increased cardiac filling pressures, and reduced contractility (CHF pigs). Arterial plasma ET-1 levels in the CHF pigs were increased 4-fold compared to sham pigs (P<0.001). Single-bolus multiple indicator-dilution experiments revealed that pulmonary synthesis and release of ET-1 was increased in CHF, while pulmonary clearance of plasma ET-1 remained unaltered despite significant reduction of pulmonary fractional extraction of plasma ET-1. Pulmonary ECE-1 isozyme activity (pmol·min−1·mg protein−1) was selectively increased in lower lobe segments of CHF pigs (2.0±0.3) compared to lower lobe segments of controls (1.1±0.1,P<0.02), and to upper lobe segments of CHF pigs (1.1±0.1,P<0.005), and correlated significantly with the wet/dry weight ratios of the pulmonary tissue samples (R=0.75,P<0.001), i.e. a marker of pulmonary congestion. Furthermore, alveolar macrophages in congested lobe segments were identified as likely sites of increased synthesis and release of ET-1.Conclusions:In rapid pacing-induced CHF, a complex cardiopulmonary interaction revealed by pulmonary congestion causes increased pulmonary production and secretion of ET-1 due to enhanced pulmonary ECE-1 activities. Pulmonary secretion of ET-1 during evolving CHF is an important contributor to elevated plasma ET-1 levels in the systemic circulation.
心力衰竭中肺内皮素转换酶的表达和活性：与内皮素生物合成和受体分布的关系。
影响因子：
6
作者：
Ergul,A;Grubbs,AL;Zhang,Y;Joffs,C;Sample,JA;King,MK;Spinale,FG
通讯作者：
Spinale,FG