Mechanical transduction of nitric oxide synthesis in the beating heart
Mechanical transduction of nitric oxide synthesis in the beating heart
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DOI：
10.1161/01.res.81.3.372
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发表时间：
1997-09-01
影响因子：
20.1
通讯作者：
Malinski, T
中科院分区：
文献类型：
--
作者：
Pinsky, DJ;Patton, S;Malinski, T
NO改变心脏的收缩和舒张特性。然而，目前尚不清楚心室负荷条件的变化是否会影响心脏NO的合成。为了了解这种潜在的收缩-舒张自动调节机制，使用放置在左心室心肌中的卟啉传感器在体内测量响应于机械刺激的心脏NO的产生。跳动的兔子心脏显示[NO]的周期性变化，在靠近内皮细胞的2.7 +/- 0.1 μ mol/L和在中心室心肌的0.93 +/- 0.20 μ mol/L处达到峰值（在大鼠心脏中浓度低15 +/- 4%）。在本研究中，我们第一次证明，增加或减少心室前负荷在体内其次是平行的变化[NO]，这可能是一种新的自动调节机制，以调整心脏的性能或灌注的心跳到心跳的基础上。为了量化施加的力和NO合成之间的关系，施加到离体非跳动心脏的间歇性压缩力或扩张力被证明会引起NO合成的爆发，峰值[NO]与心室跨壁压线性相关。裸露的心脏内皮细胞和内皮细胞消除NO信号的实验表明，这些细胞将机械刺激转化为心脏中的NO产生。总之，这些研究可能有助于解释负荷依赖性舒张，心脏记忆的机械事件之前的心跳，与心肌扩张，心肌灌注的自动调节相关的疾病，并防止血栓形成的湍流环境中跳动的心脏。
NO alters contractile and relaxant properties of the heart. However, it is not known whether changes in ventricular loading conditions affect cardiac NO synthesis. To understand this potential contractile-relaxant autoregulatory mechanism, production of cardiac NO in response to mechanical stimuli was measured in vivo using a porphyrinic sensor placed in the left ventricular myocardium. The beating rabbit heart exhibited cyclic changes in [NO], peaking at 2.7 +/- 0.1 mu mol/L near the endocardium and 0.93 +/- 0.20 mu mol/L in the midventricular myocardium (concentrations were 15 +/- 4% lower in the rat heart). In the present study, we demonstrate for the first time that increasing or decreasing ventricular preload in vivo is followed by parallel changes in [NO], which may represent a novel autoregulatory mechanism to adjust cardiac performance or perfusion on a beat-to-beat basis. To quantify the relationship between applied force and NO synthesis, intermittent compressive or distending forces applied to ex vivo nonbeating hearts were shown to cause bursts of NO synthesis, with peak [NO] linearly related to ventricular transmural pressure. Experiments in which denuding cardiac endothelial and endocardial cells abrogated the NO signal indicate that these cells transduce mechanical stimulation into NO production in the heart. Taken together, these studies may help explain load-dependent relaxation, cardiac memory for mechanical events of preceding beats, diseases associated with myocardial distension, autoregulation of myocardial perfusion, and protection from thrombosis in the turbulent flow environment within the beating heart.