Kobzik L, Reid M B, Bredt D S, Stamler J S
Department of Pathology, Brigham and Women's Hospital, Boston Massachusetts 02115.
Nature. 1994 Dec 8;372(6506):546-8. doi: 10.1038/372546a0.
Reactive oxygen intermediates modulate skeletal muscle contraction, but little is known about the role of nitric oxide (NO). Here we show that rat skeletal muscle expresses neuronal-type NO synthase and that activity varies among several respiratory and limb muscles. Immunohistochemistry showed prominent staining of type II (fast) fibre cell membranes with antibodies against neuronal-type NO synthase. NO synthase activity in muscles correlated with type II fibre density. Resting diaphragm muscle produced detectable NO chi, but no reactive oxygen intermediates. In contrast, actively contracting muscle generated increased levels of reactive oxygen intermediates. Contractile function was augmented by blockers of NO synthase, extracellular NO chelation, and guanylyl cyclase inhibition; it was depressed by NO donors and by increased levels of cyclic GMP. Force-frequency plots of different muscles showed an inverse correlation between NO synthase activity and force development. Our results support two physiological functions of NO in skeletal muscle. The first is to promote relaxation through the cGMP pathway. The second is to modulate increases in contraction that are dependent on reactive oxygen intermediates and which are thought to occur through reactions with regulatory thiols on the sarcoplasmic reticulum.
活性氧中间体可调节骨骼肌收缩，但对于一氧化氮（NO）的作用却知之甚少。在此我们表明，大鼠骨骼肌表达神经元型一氧化氮合酶，且其活性在几种呼吸肌和肢体肌肉中有所不同。免疫组织化学显示，用抗神经元型一氧化氮合酶抗体对II型（快）纤维细胞膜进行染色时，染色明显。肌肉中的一氧化氮合酶活性与II型纤维密度相关。静息的膈肌可产生可检测到的NO，但不产生活性氧中间体。相反，主动收缩的肌肉会产生增加水平的活性氧中间体。一氧化氮合酶抑制剂、细胞外NO螯合和鸟苷酸环化酶抑制可增强收缩功能；NO供体和环磷酸鸟苷水平升高则会抑制收缩功能。不同肌肉的力-频率图显示，一氧化氮合酶活性与力的产生呈负相关。我们的结果支持NO在骨骼肌中的两种生理功能。第一种是通过cGMP途径促进舒张。第二种是调节依赖于活性氧中间体的收缩增加，这种增加被认为是通过与肌浆网上的调节性硫醇反应而发生的。
