Inhibition of Na+ /K+ -ATPase and KIR channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans.

Exercise 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 (O2 saturation ∼80%). Compared to control, combined inhibition of NO, PGs, Na+ /K+ -ATPase and KIR channels (l-NMMA + ketorolac + ouabain + BaCl2; Protocol 1; n = 10) blunted the compensatory increase in FBF during HypEx by ∼50% (29 ± 6 mL min-1 vs. 62 ± 8 mL min-1 , respectively, P < 0.05). By contrast, ouabain + BaCl2 alone (Protocol 2; n = 10) did not affect this augmented hyperaemic response (50 ± 11 mL min-1 vs. 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 KIR channels is involved in the hyperaemic response to hypoxia at rest, although it does not contribute to the augmented exercise hyperaemia during hypoxia in humans.