Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium.
Inducible nitric oxide synthase inhibits oxygen consumption in collateral-dependent myocardium.
复制标题
诱导型一氧化氮合酶抑制侧支依赖性心肌的耗氧量。
DOI：
10.1152/ajpheart.00308.2013
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Bache,RobertJ
中科院分区：
文献类型：
--
作者：
Chen,Yingjie;Zhang,Ping;Li,Jingxin;Xu,Xin;Bache,RobertJ
冠状动脉闭塞后，侧支血管的生长可以为依赖的心肌提供有效的血液供应。缺血导致侧支血管的生长，引发炎症反应，细胞因子和生长因子的表达，血管内皮细胞内皮型一氧化氮合酶(ENOS)的上调，以及血管和心肌细胞中诱导型一氧化氮合酶(INOS)的表达。由于NO是一种有效的侧支血管扩张剂，因此本研究考察了iNOS或结构性NOS来源的NO是否调节侧支循环区域的心肌血流量(MBF)。非选择性抑制一氧化氮合酶可引起血管收缩，运动时侧支循环血流量明显减少。相反，高选择性iNOS抑制剂1400W使侧支循环血流量增加21±5%。选择性诱导型一氧化氮合酶阻断后MBF的增加与心肌耗氧量(MV̇O2)的增加成比例。结果提示，诱导型一氧化氮合酶产生的NO抑制侧索区的MV-̇O2，提示诱导型一氧化氮合酶阻断后MBF的增加是代谢血管扩张继发于MV-̇-O2增加的结果。因此，iNOS的协同表达抑制MV、̇O2和eNOS维持侧支血管扩张，从而优化O2供需关系，保护侧支心肌免受缺血的影响。
Following coronary artery occlusion growth of collateral vessels can provide an effective blood supply to the dependent myocardium. The ischemia, which results in growth of collateral vessels, recruits an inflammatory response with expression of cytokines and growth factors, upregulation of endothelial nitric oxide (NO) synthase (eNOS) in vascular endothelial cells, and expression of inducible nitric oxide synthase (iNOS) in both vessels and cardiac myocytes. Because NO is a potent collateral vessel dilator, this study examined whether NO derived from iNOS or constitutive NOS regulates myocardial blood flow (MBF) in the collateral region. Nonselective NOS inhibition withNG-nitro-l-arginine (LNA) caused vasoconstriction with a significant decrease in MBF to the collateral region during exercise. In contrast, the highly selective iNOS inhibitor 1400W caused a 21 ± 5% increase of MBF in the collateral region. This increase in MBF following selective iNOS blockade was proportionate to an increase in myocardial O2consumption (MV̇o2). The results suggest that NO produced by iNOS inhibits MV̇o2in the collateralized region, so that the increase in MBF following iNOS blockade was the result of metabolic vasodilation secondary to an increase in MV̇o2. Thus the coordinated expression of iNOS to restrain MV̇o2and eNOS to maintain collateral vasodilation act to optimize the O2supply-demand relationship and protect the collateralized myocardium from ischemia.