Contribution of KIR Channels and the Na+/K+‐ATPase to Local Vasodilation During Mild and Heavy Intensity Exercise in Humans

Abstract

Potassium released from repolarizing skeletal muscle elicits vasodilation by stimulating inwardly‐rectifying K+ (KIR) channels and the Na+/K+‐ATPase on the vasculature, which can serve as a feedforward mechanism to increase muscle blood flow in proportion to the degree of muscle fiber recruitment during exercise. We tested the hypothesis that KIR channels and the Na+/K+‐ATPase play a greater role in the vasodilatory response to exercise at higher contraction intensities which require greater muscle fiber recruitment. Healthy volunteers performed mild and heavy intensity rhythmic handgrip exercise using a dynamic pulley system to lift a load equivalent to 10% or 25% of maximal voluntary contraction (MVC) at a rate of 20 contractions per minute. We measured muscle activation (electromyography; EMG), forearm blood flow (FBF; Doppler ultrasound) and mean arterial pressure (MAP; brachial artery catheter) to calculate vascular conductance (FVC; FBF/MAP*100) during 5 min of forearm exercise at each intensity. Responses were assessed during 1) control conditions, 2) local inhibition of either KIR channels alone (Protocol 1; intra‐arterial BaCl2) or the Na+/K+‐ATPase alone (Protocol 2; intra‐arterial ouabain; OUA), and 3) combined inhibition of KIR channels and the Na+/K+‐ATPase (Protocols 1 & 2; BaCl2 + OUA). As expected, muscle activation was greater during heavy compared to mild exercise (Control EMG, 65 ± 6 vs. 32 ± 3% of MVC; P < 0.05). In Protocol 1 (4 women, 5 men; 26 ± 1 yrs), BaCl2 reduced steady‐state FVC by −62 ± 21 ml/min/100 mmHg during mild exercise (Control: 170 ± 27 vs. BaCl2: 107 ± 10 ml/min/100 mmHg; P < 0.05), and combined inhibition with BaCl2 + OUA had no further effect (Δ FVC from Control, −67 ± 20; FVC, 103 ± 11 ml/min/100 mmHg; P = NS vs. BaCl2 alone). During heavy intensity exercise, BaCl2 reduced FVC by −59 ± 13 ml/min/100 mmHg (Control: 333 ± 24 vs. BaCl2: 274 ± 29 ml/min/100 mmHg; P < 0.05), which was similar to the effect of BaCl2 during mild exercise (Δ FVC P = NS vs. mild exercise). However, in contrast to mild exercise, combined inhibition with BaCl2 + OUA further attenuated FVC during heavy intensity exercise (Δ FVC from Control, □108 ± 24; FVC, 225 ± 15 ml/min/100 mmHg; P < 0.05 vs. BaCl2). In Protocol 2 (2 women, 3 men; 26 ± 2 yrs), OUA alone had no effect on FVC during mild exercise (Δ FVC from Control, −2 ± 6; FVC, Control: 141 ± 31 vs. OUA: 139 ± 36; P = NS) or heavy exercise (Δ FVC from Control, −11 ± 11; FVC, Control: 325 ± 70 vs. OUA: 313 ± 71; P = NS), whereas combined inhibition with BaCl2 + OUA reduced FVC to a similar extent as in Protocol 1 (mild exercise, Δ FVC from Control: −43 ± 4; FVC: 98 ± 30; heavy exercise, Δ FVC from Control: −109 ± 16; FVC: 216 ± 66 ml/min/100 mmHg, both P < 0.05 vs. Control and OUA alone). We conclude that KIR channel activation contributes similarly to skeletal muscle vascular tone at mild and heavy exercise intensities. Furthermore, an obligatory role for Na+/K+‐ATPase in vascular control is not revealed until KIR channels are inhibited during heavy intensity exercise.Support or Funding InformationNIH R01‐HL119337