Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.
Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.
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缺氧期间急性亚硝酸盐输注对原位离体骨骼肌收缩经济和代谢的影响。
DOI：
10.1113/jp279789
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发表时间：
2020
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：
Porcelli,Simone;Rasica,Letizia;Ferguson,BrianS;Kavazis,AndreasN;McDonald,James;Hogan,MichaelC;Grassi,Bruno;Gladden,LBruce
要点血浆亚硝酸盐浓度升高可能对骨骼肌功能有有益影响。解释这些观察的生理学基础尚未明确，可能涉及对肌肉收缩力量、微血管氧气输送和骨骼肌氧化代谢的积极影响。在犬离体腓肠肌模型中，我们评估了急性亚硝酸盐输注对肌力和骨骼肌氧化代谢的影响。在低氧条件下，但在正常对流氧气输送的情况下，血浆亚硝酸盐浓度升高既不影响肌肉力量，也不影响肌肉收缩经济。与先前的结果一致，即在高度氧化和高度灌流的肌肉中，硝酸盐/亚硝酸盐的应用有限或没有影响。我们的数据表明，线粒体呼吸、线粒体NOR肌力的产生不受缺氧时NO前体浓度急剧升高的影响。摘要关于增强型一氧化氮(NO)对骨骼肌力产生和氧耗的影响，已有相反的研究结果报道。本研究检测了在亚硝酸盐输注的低氧(但正常的对流氧气输送)过程中，骨骼肌的线粒体呼吸和收缩经济性。对犬在体腓肠肌(n=8)进行电刺激等长强直收缩3分钟，∼为35%。在收缩过程中，将亚硝酸钠(亚硝酸盐)或氯化钠(生理盐水)注入月国动脉。是根据菲克原理计算出来的。实验是在低氧条件下进行的(F=0.12)，而对流氧气输送在两种情况下都通过泵驱动的血流()维持在正常水平。取肌肉活检，呼吸计量法测定线粒体呼吸。亚硝酸盐输注显著提高了血浆中亚硝酸盐和硝酸盐的浓度。在不同的条件下，没有观察到力的差异。亚硝酸盐(6.1g/ml100 mg−1min−1)和生理盐水(6.2g±91.8mL100 mg−1min−1)之间没有显著差异，即使在每单位发达力量(肌肉收缩经济)被归一化后也是如此。在ADP刺激的线粒体最大呼吸(包括络合物I和络合物II)、泄漏呼吸和氧化磷酸化偶联的条件之间没有发现差异。总而言之，在对流输氧量没有改变的情况下，肌力、肌肉收缩经济性和线粒体呼吸不受亚硝酸盐急性输注的影响。先前报道的血浆亚硝酸盐浓度升高的积极影响可能是通过增加微血管氧气利用率来实现的。
Key pointsIncreased plasma nitrite concentrations may have beneficial effects on skeletal muscle function.The physiological basis explaining these observations has not been clearly defined and it may involve positive effects on muscle contraction force, microvascular O2delivery and skeletal muscle oxidative metabolism.In the isolated canine gastrocnemius model, we evaluated the effects of acute nitrite infusion on muscle force and skeletal muscle oxidative metabolism.Under hypoxic conditions, but in the presence of normal convective O2delivery, an elevated plasma nitrite concentration affects neither muscle force, nor muscle contractile economy.In accordance with previous results suggesting limited or no effects of nitrate/nitrite administrations in highly oxidative and highly perfused muscle, our data suggest that neither mitochondrial respiration, nor muscle force generation are affected by acute increased concentrations of NO precursors in hypoxia.AbstractContrasting findings have been reported concerning the effects of augmented nitric oxide (NO) on skeletal muscle force production and oxygen consumption (). The present study examined skeletal muscle mitochondrial respiration and contractile economy in an isolated muscle preparation during hypoxia (but normal convective O2delivery) with nitrite infusion. Isolated canine gastrocnemius musclesin situ(n= 8) were studied during 3 min of electrically stimulated isometric tetanic contractions corresponding to ∼35% of . During contractions, sodium nitrite (NITRITE) or sodium chloride (SALINE) was infused into the popliteal artery. was calculated from the Fick principle. Experiments were carried out in hypoxia ( = 0.12), whereas convective O2delivery was maintained at normal levels under both conditions by pump‐driven blood flow (). Muscle biopsies were taken and mitochondrial respiration was evaluated by respirometry. Nitrite infusion significantly increased both nitrite and nitrate concentrations in plasma. No differences in force were observed between conditions. was not significantly different between NITRITE (6.1 ± 1.8 mL100 g−1min−1) and SALINE (6.2 ± 1.8 mL 100 g−1min−1), even after being ‘normalized’ per unit of developed force (muscle contractile economy). No differences between conditions were found for maximal ADP‐stimulated mitochondrial respiration (both for complex I and complex II), leak respiration and oxidative phosphorylation coupling. In conclusion, in the absence of changes in convective O2delivery, muscle force, muscle contractile economy and mitochondrial respiration were not affected by acute infusion of nitrite. The previously reported positive effects of elevated plasma nitrite concentrations are presumably mediated by the increased microvascular O2availability.