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  • Title: Acute inhibition of ATP-sensitive K+ channels impairs skeletal muscle vascular control in rats during treadmill exercise.
    Author: Holdsworth CT, Copp SW, Ferguson SK, Sims GE, Poole DC, Musch TI.
    Journal: Am J Physiol Heart Circ Physiol; 2015 Jun 01; 308(11):H1434-42. PubMed ID: 25820394.
    Abstract:
    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.
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