Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
J Physiol. 2020 Oct;598(19):4357-4369. doi: 10.1113/JP280027. Epub 2020 Aug 16.
Respiratory muscle function declines with ageing, contributing to breathing complications in the elderly. Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO for 14 days compared with age-matched controls. Myofibrillar protein phosphorylation, which enhances contractile function, did not change in our study - a finding inconsistent with the hypothesis that this post-translational modification is a mechanism for dietary nitrate to improve muscle contractile function. Nitrate supplementation did not change the abundance of calcium-handling proteins in the diaphragm of old mice, in contrast with findings from the limb muscles of young mice in previous studies. Our findings suggest that nitrate supplementation enhances myofibrillar protein function without affecting the phosphorylation status of key myofibrillar proteins.
Inspiratory muscle (diaphragm) function declines with age, contributing to ventilatory dysfunction, impaired airway clearance, and overall decreased quality of life. Diaphragm isotonic and isometric contractile properties are reduced with ageing, including maximal specific force, shortening velocity and peak power. Contractile properties of limb muscle in both humans and rodents can be improved by dietary nitrate supplementation, but effects on the diaphragm and mechanisms behind these improvements remain poorly understood. One potential explanation underlying the nitrate effects on contractile properties is increased phosphorylation of myofibrillar proteins, a downstream outcome of nitrate reduction to nitrite and nitric oxide. We hypothesized that dietary nitrate supplementation would improve diaphragm contractile properties in aged mice. To test our hypothesis, we measured the diaphragm function of old (24 months) mice allocated to 1 mm NaNO in drinking water for 14 days (n = 8) or untreated water (n = 6). The maximal rate of isometric force development (∼30%) and peak power (40%) increased with nitrate supplementation (P < 0.05). There were no differences in the phosphorylation status of key myofibrillar proteins and abundance of Ca-release proteins in nitrate vs. control animals. In general, our study demonstrates improved diaphragm contractile function with dietary nitrate supplementation and supports the use of this strategy to improve inspiratory function in ageing populations. Additionally, our findings suggest that dietary nitrate improves diaphragm contractile properties independent of changes in abundance of Ca-release proteins or phosphorylation of myofibrillar proteins.
呼吸肌功能随年龄增长而下降，导致老年人呼吸并发症。在这里，我们报告说，与年龄匹配的对照组相比，接受补充 NaNO 治疗 14 天的老年小鼠的体外呼吸肌收缩功能更强。在我们的研究中，肌球蛋白磷酸化没有改变，这一发现与这种翻译后修饰是饮食硝酸盐改善肌肉收缩功能的机制的假设不一致。硝酸盐补充剂并没有改变老年小鼠膈肌中钙处理蛋白的丰度，这与以前研究中年轻小鼠四肢肌肉的发现不同。我们的研究结果表明，硝酸盐补充剂增强了肌球蛋白纤维的功能，而不影响关键肌球蛋白纤维蛋白的磷酸化状态。
吸气肌（膈肌）功能随年龄增长而下降，导致通气功能障碍、气道清除能力受损以及整体生活质量下降。膈肌等长和等张收缩性能随年龄增长而降低，包括最大比力、缩短速度和峰值功率。饮食硝酸盐补充剂可改善人类和啮齿动物的四肢肌肉收缩性能，但对膈肌的影响及其改善的机制仍知之甚少。硝酸盐对收缩性能的影响的一个潜在解释是肌球蛋白蛋白的磷酸化增加，这是硝酸盐还原为亚硝酸盐和一氧化氮的下游结果。我们假设饮食硝酸盐补充剂会改善老年小鼠的膈肌收缩性能。为了验证我们的假设，我们测量了分配到饮用水中 1mm NaNO 14 天（n=8）或未处理水（n=6）的老年（24 个月）小鼠的膈肌功能。与对照组相比，等速和等长力的最大发展速率（约 30%）和峰值功率（40%）随着硝酸盐的补充而增加（P<0.05）。在硝酸盐与对照组动物中，关键肌球蛋白蛋白的磷酸化状态和 Ca 释放蛋白的丰度没有差异。总的来说，我们的研究表明，饮食硝酸盐补充剂可改善膈肌收缩功能，并支持将这种策略用于改善老龄化人群的吸气功能。此外，我们的研究结果表明，饮食硝酸盐改善了膈肌的收缩性能，而不改变 Ca 释放蛋白的丰度或肌球蛋白纤维蛋白的磷酸化。
