Paulus Walter J, Bronzwaer Jean G F
Institute for Cardiovascular Research, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Am J Physiol Heart Circ Physiol. 2004 Jul;287(1):H8-13. doi: 10.1152/ajpheart.01147.2003.
Beneficial actions of nitric oxide (NO) in failing myocardium have frequently been overshadowed by poorly documented negative inotropic effects mainly derived from in vitro cardiac preparations. NO's beneficial actions include control of myocardial energetics and improvement of left ventricular (LV) diastolic distensibility. In isolated cardiomyocytes, administration of NO increases their diastolic cell length consistent with a rightward shift of the passive length-tension relation. This shift is explained by cGMP-induced phosphorylation of troponin I, which prevents calcium-independent diastolic cross-bridge cycling and concomitant diastolic stiffening of the myocardium. Similar improvements in diastolic stiffness have been observed in isolated guinea pig hearts, in pacing-induced heart failure dogs, and in patients with dilated cardiomyopathy or aortic stenosis and have been shown to result in higher LV preload reserve and stroke work. NO also controls myocardial energetics through its effects on mitochondrial respiration, oxygen consumption, and substrate utilization. The effects of NO on diastolic LV performance appear to be synergistic with its effects on myocardial energetics through prevention of myocardial energy wastage induced by LV contraction against late-systolic reflected arterial pressure waves and through prevention of diastolic LV stiffening, which is essential for the maintenance of adequate subendocardial coronary perfusion. A drop in these concerted actions of NO on diastolic LV distensibility and on myocardial energetics could well be instrumental for the relentless deterioration of failing myocardium.
一氧化氮（NO）在衰竭心肌中的有益作用常常被主要源于体外心脏标本的、记录不充分的负性肌力作用所掩盖。NO的有益作用包括控制心肌能量代谢和改善左心室（LV）舒张期扩张性。在分离的心肌细胞中，给予NO可增加其舒张期细胞长度，这与被动长度-张力关系的右移一致。这种右移是由cGMP诱导的肌钙蛋白I磷酸化所解释的，它可防止钙非依赖性舒张期横桥循环以及随之而来的心肌舒张期僵硬。在分离的豚鼠心脏、起搏诱导的心力衰竭犬以及扩张型心肌病或主动脉瓣狭窄患者中也观察到了舒张期僵硬的类似改善，并且已证明这会导致更高的左心室前负荷储备和搏功。NO还通过其对线粒体呼吸、氧消耗和底物利用的影响来控制心肌能量代谢。NO对左心室舒张期性能的影响似乎与其对心肌能量代谢的影响具有协同作用，这是通过防止左心室收缩对抗收缩期末期反射动脉压力波所诱导的心肌能量浪费以及通过防止左心室舒张期僵硬来实现的，而左心室舒张期僵硬对于维持足够的心内膜下冠状动脉灌注至关重要。NO在左心室舒张期扩张性和心肌能量代谢方面的这些协同作用的下降很可能是衰竭心肌持续恶化的原因。
