Kumar Ravi, Coggan Andrew R, Ferreira Leonardo F
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.
Department of Kinesiology, Indiana University Purdue University, Indianapolis, IN, USA.
Nitric Oxide. 2022 May 1;122-123:54-61. doi: 10.1016/j.niox.2022.04.001. Epub 2022 Apr 8.
Nitric oxide (NO) is complex modulator of skeletal muscle contractile function, capable of increasing or decreasing force and power output depending on multiple factors. This review explores the effects and potential mechanisms for modulation of skeletal muscle contractile function by NO, from pharmacological agents in isolated muscle preparations to dietary nitrate supplementation in humans and animals. Pharmacological manipulation in vitro suggests that NO signaling diminishes submaximal isometric force, whereas dietary manipulation in vivo suggest that NO enhances submaximal force. The bases for these different responses are unknown but could reflect dose-dependent effects. Maximal isometric force is unaffected by physiologically relevant levels of NO, which do not induce overt protein oxidation. Pharmacological and dietary manipulation of NO signaling enhances the maximal rate of isometric force development, unloaded shortening velocity, and peak power. We hypothesize that these effects are mediated by post-translational modifications of myofibrillar proteins that modulate thick filament regulation of contraction (e.g., mechanosensing and strain-dependence of cross-bridge kinetics). NO effects on contractile function appear to have some level of fiber type and sex-specificity. The mechanisms behind NO-mediated changes in skeletal muscle function need to be explored through proteomics analysis and advanced biophysical assays to advance the development of small molecules and open intriguing therapeutic and ergogenic possibilities for aging, disease, and athletic performance.
一氧化氮（NO）是骨骼肌收缩功能的复杂调节剂，根据多种因素，它能够增加或降低力量及功率输出。本综述探讨了NO对骨骼肌收缩功能调节的作用及潜在机制，范围从分离肌肉制剂中的药物制剂到人和动物的膳食硝酸盐补充。体外药理学操作表明，NO信号传导会降低次最大等长力，而体内膳食操作表明，NO会增强次最大力。这些不同反应的基础尚不清楚，但可能反映了剂量依赖性效应。最大等长力不受生理相关水平NO的影响，这些水平不会诱导明显的蛋白质氧化。对NO信号传导的药理学和膳食操作可提高等长力发展的最大速率、无负荷缩短速度和峰值功率。我们假设这些效应是由肌原纤维蛋白的翻译后修饰介导的，这些修饰调节收缩的粗肌丝调节（例如，横桥动力学的机械传感和应变依赖性）。NO对收缩功能的影响似乎具有一定程度的纤维类型和性别特异性。需要通过蛋白质组学分析和先进的生物物理测定来探索NO介导的骨骼肌功能变化背后的机制，以推动小分子的开发，并为衰老、疾病和运动表现开辟有趣的治疗和促力可能性。
