Myocardial contractile effects of nitric oxide.
Myocardial contractile effects of nitric oxide.
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DOI：
10.1023/a:1020754232359
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发表时间：
2002-10-01
影响因子：
4.6
通讯作者：
Bronzwaer, Jean G F
中科院分区：
文献类型：
--
作者：
Paulus, Walter J;Bronzwaer, Jean G F
最近的实验和临床研究解决了围绕NO的心肌收缩作用的一些争议。这些争议是：(1)NO在基线时是否发挥收缩作用？(2)NO是正性抑或负性肌力作用？(3)当NO来自NO供体或来自不同亚型的一氧化氮合酶(NOS)时，NO的收缩作用相似吗？(4)在肥厚、衰竭或缺血的心肌中，NO没有同样的作用吗？心脏选择性过表达一氧化氮合酶的转基因小鼠发现，一氧化氮主要通过肌膜脱敏产生基础发展的左心室压力的轻微降低和左心室的松弛加速效应。此前，在离体鼠心脏和人类冠脉内输注NO供体的过程中也有类似的发现。LV松弛加速效应伴随着舒张期LV扩张性的增加，这增加了LV前负荷储备，尤其是在心力衰竭患者。这种对舒张期左心室功能的有益影响总是盖过了在整体左心室性能方面由NO引起的左心室发展压的小的衰减。在大多数实验和临床条件下，当NO来自于NO供体或由不同亚型的NOS产生时，NO的收缩作用是相似的。由于诱导型一氧化氮合酶(NOS2)的表达经常伴随着氧化应激的升高，因此NOS2产生的NO可导致过氧亚硝酸盐诱导的收缩功能损害，如在缺血或败血症心肌中观察到的那样。最后，肌丝异构体或浓度的改变可以影响NO介导的肌纤维脱敏，并改变肥厚或衰竭心肌中NO的心肌收缩效应。
Recent experimental and clinical research solved some of the controversies surrounding the myocardial contractile effects of NO. These controversies were: (1) does NO exert a contractile effect at baseline? (2) is NO a positive or a negative inotrope? (3) Are the contractile effects of NO similar when NO is derived from NO-donors or from the different isoforms of NO synthases (NOS)? (4) Does NO exert the same effects in hypertrophied, failing or ischemic myocardium? Transgenic mice with cardioselective overexpression of NOS revealed NO to produce a small reduction in basal developed LV pressure and a LV relaxation-hastening effect mainly through myofilamentary desensitization. Similar findings had previously been reported during intracoronary infusions of NO-donors in isolated rodent hearts and in humans. The LV relaxation hastening effect was accompanied by increased diastolic LV distensibility, which augmented LV preload reserve especially in heart failure patients. This beneficial effect on diastolic LV function always overrode the small NO-induced attenuation in LV developed pressure in terms of overall LV performance. In most experimental and clinical conditions, contractile effects of NO were similar when NO was derived from NO-donors or produced by the different isoforms of NOS. Because expression of inducible NOS (NOS2) is frequently accompanied by elevated oxidative stress, NO produced by NOS2 can lead to peroxynitrite-induced contractile impairment as observed in ischemic or septic myocardium. Finally, shifts in isoforms or in concentrations of myofilaments can affect NO-mediated myofilamentary desensitization and alter the myocardial contractile effects of NO in hypertrophied or failing myocardium.