Colburn Trenton D, Ferguson Scott K, Holdsworth Clark T, Craig Jesse C, Musch Timothy I, Poole David C
Department of Kinesiology, Kansas State University, Manhattan, Kansas; and.
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas.
J Appl Physiol (1985). 2017 Jan 1;122(1):153-160. doi: 10.1152/japplphysiol.00367.2016. Epub 2016 Oct 27.
Exercise intolerance characteristic of diseases such as chronic heart failure (CHF) and diabetes is associated with reduced nitric oxide (NO) bioavailability from nitric oxide synthase (NOS), resulting in an impaired microvascular O driving pressure (Pomv; O delivery/O utilization) and metabolic control. Infusions of the potent NO donor sodium nitroprusside augment NO bioavailability yet decrease mean arterial pressure (MAP) thereby reducing its potential efficacy for patient populations. To eliminate or reduce hypotensive sequelae, [Formula: see text] was superfused onto the spinotrapezius muscle. It was hypothesized that local [Formula: see text] administration would elevate resting Pomv and slow Pomv kinetics [increased time constant (τ) and mean response time (MRT)] following the onset of muscle contractions without decreasing MAP. In 12 anesthetized male Sprague-Dawley rats, Pomv of the circulation-intact spinotrapezius muscle was measured by phosphorescence quenching during 180 s of electrically induced twitch contractions (1 Hz) before and after superfusion of sodium nitrite (NaNO 30 mM). [Formula: see text] superfusion elevated resting Pomv (control: 28.4 ± 1.1 vs. [Formula: see text]: 31.6 ± 1.2 mmHg; P ≤ 0.05), τ (control: 12.3 ± 1.2 vs. [Formula: see text]: 19.7 ± 2.2 s; P ≤ 0.05), and MRT (control: 19.3 ± 1.9 vs. [Formula: see text]: 25.6 ± 3.3 s; P ≤ 0.05). Importantly, these effects occurred in the absence of any reduction in MAP (103 ± 4 vs. 105 ± 4 mmHg, pre- and postsuperfusion respectively; P > 0.05). These results indicate that [Formula: see text] supplementation delivered to the muscle directly through [Formula: see text] superfusion enhances the blood-myocyte oxygen driving pressure without compromising MAP at rest and following the onset of muscle contraction. This strategy has substantial clinical utility for a range of ischemic conditions.
NEW & NOTEWORTHY: Ischemic conditions as diverse as chronic heart failure (CHF) and frostbite inflict tissue damage via inadequate O delivery. Herein we demonstrate that direct application of sodium nitrite enhances the O supply-O demand relationship, raising microvascular O pressure in healthy skeletal muscle. This therapeutic action of nitrite-derived nitric oxide occurred without inducing systemic hypotension and has the potential to relieve focal ischemia and preserve tissue vitality by enhancing O delivery.
诸如慢性心力衰竭（CHF）和糖尿病等疾病所特有的运动不耐受与一氧化氮合酶（NOS）产生的一氧化氮（NO）生物利用度降低有关，导致微血管氧驱动压力（Pomv；氧输送/氧利用）受损和代谢控制不良。强力NO供体硝普钠的输注可提高NO生物利用度，但会降低平均动脉压（MAP），从而降低其对患者群体的潜在疗效。为了消除或减少低血压后遗症，将[化学式：见正文]灌注到斜方肌上。据推测，局部给予[化学式：见正文]会提高静息Pomv，并减缓肌肉收缩开始后Pomv的动力学变化[增加时间常数（τ）和平均反应时间（MRT）]，而不会降低MAP。在12只麻醉的雄性Sprague-Dawley大鼠中，在灌注亚硝酸钠（NaNO₂ 30 mM）之前和之后，通过磷光猝灭法在180秒的电诱发抽搐收缩（1 Hz）期间测量完整循环的斜方肌的Pomv。[化学式：见正文]灌注提高了静息Pomv（对照组：28.4±1.1 vs. [化学式：见正文]组：31.6±1.2 mmHg；P≤0.05）、τ（对照组：12.3±1.2 vs. [化学式：见正文]组：19.7±2.2秒；P≤0.05）和MRT（对照组：19.3±1.9 vs. [化学式：见正文]组：25.6±3.3秒；P≤0.05）。重要的是，这些效应在MAP没有任何降低的情况下发生（分别在灌注前和灌注后为103±4 vs. 105± mmHg；P>0.05）。这些结果表明，通过[化学式：见正文]灌注直接输送到肌肉的[化学式：见正文]补充剂可增强血液-心肌细胞氧驱动压力，而不会在静息时和肌肉收缩开始后损害MAP。该策略对一系列缺血性疾病具有重要的临床应用价值。
诸如慢性心力衰竭（CHF）和冻伤等多种缺血性疾病通过氧输送不足导致组织损伤。在此我们证明，直接应用亚硝酸钠可增强氧供应-氧需求关系，提高健康骨骼肌中的微血管氧压力。亚硝酸盐衍生的一氧化氮的这种治疗作用在不引起全身性低血压的情况下发生，并且有可能通过增强氧输送来缓解局部缺血并维持组织活力。
