Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ.
Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ.
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L-NAME 抑制一氧化氮合酶对离体犬肌肉原位吸氧动力学的影响。
DOI：
10.1113/jphysiol.2005.090068
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Gladden,LBruce
中科院分区：
文献类型：
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作者：
Grassi,Bruno;Hogan,MichaelC;Kelley,KevinM;Howlett,RichardA;Gladden,LBruce
一氧化氮（NO）在线粒体呼吸链水平上对O2摄取具有抑制作用。本研究的目的是评估一氧化氮合酶（NOS）抑制对肌肉动力学的影响。在从休息到4分钟电刺激收缩（相当于肌肉峰值的约60%）的过渡期间，研究了离体犬腓肠肌原位（n= 6）。比较了两种条件：（i）对照（CTRL）和（ii）L-NAME，其中给予NOS抑制剂L-NAME（20 mg kg−1）。在这两种情况下，肌肉都是用不断升高的血流量泵灌注的，血流量水平在自发自灌注的初步收缩试验期间测量。还输注了血管扩张药物。动脉和静脉O2浓度测定在休息和过渡期间在5-7秒的时间间隔。 根据Fick原理计算。在休息和收缩期间获得肌肉活检。连续测量肌肉力量。磷酸肌酸水解和计算的底物水平磷酸化在l-NAME中略低于（但不显著）CTRL。l ‐ NAME组的疲劳程度显著低于对照组（P< 0.05）。动力学“基本”分量的时间延迟（TDf）和时间常数（τf）在CTRL（TDf 7.2 ± 1.2 s;和τ f 10.6 ± 1.3，±s.e.m.）和l-NAME（TDf 9.3 ± 0.6;和τ f 10.4 ± 1.0）。与我们的假设相反，NOS抑制并没有加速肌肉动力学。NO对线粒体呼吸的下调并不限制运动开始时氧化代谢调节的动力学。
Nitric oxide (NO) has an inhibitory action on O2uptake at the level of the mitochondrial respiratory chain. The aim of this study was to evaluate the effects of NO synthase (NOS) inhibition on muscle kinetics. Isolated canine gastrocnemius musclesin situ(n= 6) were studied during transitions from rest to 4‐min of electrically stimulated contractions corresponding to ∼60% of the muscle peak . Two conditions were compared: (i) Control (CTRL) and (ii)l‐NAME, in which the NOS inhibitorl‐NAME (20 mg kg−1) was administered. In both conditions the muscle was pump‐perfused with constantly elevated blood flow , at a level measured during a preliminary contraction trial with spontaneous self‐perfused. A vasodilatory drug was also infused. Arterial and venous O2concentrations were determined at rest and at 5–7 s intervals during the transition. was calculated by Fick's principle. Muscle biopsies were obtained at rest and during contractions. Muscle force was measured continuously. Phosphocreatine hydrolysis and the calculated substrate level phosphorylation were slightly (but not significantly) lower inl‐NAME than in CTRL. Significantly (P< 0.05) less fatigue was found inl‐NAMEversusCTRL. The time delay (TDf) and the time constant (τf) of the ‘fundamental’ component of kinetics were not significantly different between CTRL (TDf7.2 ± 1.2 s; and τf10.6 ± 1.3, ±s.e.m.) andl‐NAME (TDf9.3 ± 0.6; and τf10.4 ± 1.0). Contrary to our hypothesis, NOS inhibition did not accelerate muscle kinetics. The down‐regulation of mitochondrial respiration by NO does not limit the kinetics of adjustment of oxidative metabolism at exercise onset.