Holdsworth Clark T, Copp Steven W, Ferguson Scott K, Sims Gabrielle E, Poole David C, Musch Timothy I
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas; and.
Am J Physiol Heart Circ Physiol. 2015 Jun 1;308(11):H1434-42. doi: 10.1152/ajpheart.00772.2014. Epub 2015 Mar 27.
The ATP-sensitive K(+) (KATP) channel is part of a class of inward rectifier K(+) channels that can link local O2 availability to vasomotor tone across exercise-induced metabolic transients. The present investigation tested the hypothesis that if KATP channels are crucial to exercise hyperemia, then inhibition via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance during treadmill exercise. In 27 adult male Sprague-Dawley rats, mean arterial pressure, blood lactate concentration, and hindlimb muscle BF (radiolabeled microspheres) were determined at rest (n = 6) and during exercise (n = 6-8, 20, 40, and 60 m/min, 5% incline, i.e., ~60-100% maximal O2 uptake) under control and GLI conditions (5 mg/kg intra-arterial). At rest and during exercise, mean arterial pressure was higher (rest: 17 ± 3%, 20 m/min: 5 ± 1%, 40 m/min: 5 ± 2%, and 60 m/min: 5 ± 1%, P < 0.05) with GLI. Hindlimb muscle BF (20 m/min: 16 ± 7%, 40 m/min: 30 ± 9%, and 60 m/min: 20 ± 8%) and vascular conductance (20 m/min: 20 ± 7%, 40 m/min: 33 ± 8%, and 60 m/min: 24 ± 8%) were lower with GLI during exercise at 20, 40, and 60 m/min, respectively (P < 0.05 for all) but not at rest. Within locomotory muscles, there was a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibers at all exercise speeds (P < 0.05). Additionally, blood lactate concentration was 106 ± 29% and 44 ± 15% higher during exercise with GLI at 20 and 40 m/min, respectively (P < 0.05). That KATP channel inhibition reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperemia.
ATP敏感性钾（KATP）通道是内向整流钾通道家族的一部分，它能够在运动诱导的代谢瞬变过程中，将局部氧气供应与血管运动张力联系起来。本研究检验了这样一个假设：如果KATP通道对运动性充血至关重要，那么通过格列本脲（GLI）进行抑制将降低跑步机运动期间后肢骨骼肌血流量（BF）和血管传导率。在27只成年雄性Sprague-Dawley大鼠中，分别在对照和GLI条件下（动脉内注射5mg/kg），于静息状态（n = 6）和运动期间（n = 6 - 8，速度为20、40和60m/min，坡度5%，即约60 - 100%最大摄氧量）测定平均动脉压、血乳酸浓度和后肢肌肉BF（放射性微球法）。在静息和运动期间，使用GLI时平均动脉压均升高（静息时：17±3%，20m/min时：5±1%，40m/min时：5±2%，60m/min时：5±1%，P < 0.05）。在运动速度为20、40和60m/min时，使用GLI后后肢肌肉BF（20m/min时：16±7%，40m/min时：30±9%，60m/min时：20±8%）和血管传导率（20m/min时：20±7%，40m/min时：33±8%，60m/min时：24±8%）分别降低（所有P < 0.05），但在静息时无此现象。在运动肌肉中，在所有运动速度下，主要由I型和IIa型纤维组成的肌肉中BF的降低比例更大（P < 0.05）。此外，在运动速度为20和40m/min时，使用GLI运动期间血乳酸浓度分别升高106±29%和44±15%（P < 0.05）。KATP通道抑制降低大鼠运动期间后肢肌肉BF，这支持了KATP通道在大量肌肉运动诱导的充血中起必要作用。
