Inhibition of Na+ /K+ -ATPase and KIR channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans.
Inhibition of Na+ /K+ -ATPase and KIR channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans.
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Na /K -ATP 酶和 KIR 通道的抑制消除了人类骨骼肌静息但不收缩时的缺氧充血。
DOI：
10.1113/jp275913
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Dinenno,FrankA
中科院分区：
文献类型：
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作者：
Racine,MatthewL;Crecelius,AnneR;Luckasen,GaryJ;Larson,DennisG;Dinenno,FrankA
关键点增加运动肌肉的血流量（充血）有助于匹配氧气输送和代谢需求。在低氧运动中，肌肉充血代偿性增加，维持氧的输送和组织氧的消耗。在低氧运动中，一氧化氮（NO）和前列腺素（PGs）约占充血增加的一半，但其余反应的贡献者尚不清楚。在本研究中，抑制NO、PGs、NO和PGs的产生，可使低氧运动中的肌肉充血增加。Na +/K +-ATP酶和内向整流钾（KIR）通道在低氧运动期间并没有减弱增强的充血，超过了先前单独使用NO/PG阻断的观察结果。此外，尽管仅抑制Na +/K +-ATP酶和KIR通道可消除休息时缺氧时的充血，但对缺氧运动时的充血增强没有影响。这是首次在人体中进行的研究，证明Na +/K +-ATP酶和KIR通道激活是休息时缺氧时肌肉充血增强所必需的，而不是在缺氧运动时。从而为血管控制提供了新的见解。AbstractExercise hyperemia in hypoxia is augmented relative to the same exercise intensity in normoxia.在中等强度的握力运动中，内皮源性一氧化氮（NO）和血管舒张性前列腺素（PG）对低氧运动（HypEx）的前臂血流（FBF）增加的反应贡献了约50%，尽管其余反应的机制尚不清楚。我们假设联合抑制NO、PGs、Na +/K +-ATP酶和内向整流钾（KIR）通道将消除HypEx中增强的充血反应。在健康的年轻人中，FBF反应进行了测量（多普勒超声）和前臂血管传导率计算在5分钟的有节奏的握力运动在20%的最大自主收缩下，在区域交感肾上腺抑制在常氧和等二氧化碳HypEx（O2饱和度超过80%）。与对照组相比，联合抑制NO、PGs、Na +/K +-ATP酶和KIR通道（1-NMMA+酮咯酸+哇巴因+BaCl2;方案1; n = 10）使HypEx期间FBF的代偿性增加减弱了约50%（29 ± 6 mL min-1 vs. 62 ± 8 mL min-1，P <0.05）。相比之下，单独使用哇巴因+氯化钡（方案2; n = 10）并不影响这种增强的充血反应（50 ± 11 mL min-1 vs. 60 ± 13 mL min-1，P> 0.05）。但两种方案的阻断条件均能消除静息时对低氧的高血反应（P <0.05）。我们的结论是，Na +/K +-ATP酶和KIR通道的激活参与了静息时对低氧的高血反应，尽管它并不有助于人类低氧期间运动性充血的增强。
Key pointsIncreasing blood flow (hyperaemia) to exercising muscle helps match oxygen delivery and metabolic demand. During exercise in hypoxia, there is a compensatory increase in muscle hyperaemia that maintains oxygen delivery and tissue oxygen consumption.Nitric oxide (NO) and prostaglandins (PGs) contribute to around half of the augmented hyperaemia during hypoxic exercise, although the contributors to the remaining response are unknown.In the present study, inhibiting NO, PGs, Na+/K+‐ATPase and inwardly rectifying potassium (KIR) channels did not blunt augmented hyperaemia during hypoxic exercise beyond previous observations with NO/PG block alone. Furthermore, although inhibition of only Na+/K+‐ATPase and KIRchannels abolished hyperaemia during hypoxia at rest, it had no effect on augmented hyperaemia during hypoxic exercise.This is the first study in humans to demonstrate that Na+/K+‐ATPase and KIRchannel activation is required for augmented muscle hyperaemia during hypoxia at rest but not during hypoxic exercise, thus providing new insight into vascular control.AbstractExercise hyperaemia in hypoxia is augmented relative to the same exercise intensity in normoxia. During moderate‐intensity handgrip exercise, endothelium‐derived nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to ∼50% of the augmented forearm blood flow (FBF) response to hypoxic exercise (HypEx), although the mechanism(s) underlying the remaining response are unclear. We hypothesized that combined inhibition of NO, PGs, Na+/K+‐ATPase and inwardly rectifying potassium (KIR) channels would abolish the augmented hyperaemic response in HypEx. In healthy young adults, FBF responses were measured (Doppler ultrasound) and forearm vascular conductance was calculated during 5 min of rhythmic handgrip exercise at 20% maximum voluntary contraction under regional sympathoadrenal inhibition in normoxia and isocapnic HypEx (O2saturation ∼80%). Compared to control, combined inhibition of NO, PGs, Na+/K+‐ATPase and KIRchannels (l‐NMMA + ketorolac + ouabain + BaCl2;Protocol 1;n= 10) blunted the compensatory increase in FBF during HypEx by ∼50% (29 ± 6 mL min−1vs. 62 ± 8 mL min−1, respectively,P< 0.05). By contrast, ouabain + BaCl2alone (Protocol 2;n= 10) did not affect this augmented hyperaemic response (50 ± 11 mL min−1vs. 60 ± 13 mL min−1, respectively,P> 0.05). However, the blocked condition in both protocols abolished the hyperaemic response to hypoxia at rest (P< 0.05). We conclude that activation of Na+/K+‐ATPase and KIRchannels is involved in the hyperaemic response to hypoxia at rest, although it does not contribute to the augmented exercise hyperaemia during hypoxia in humans.