Inhibition of Na+/K+-ATPase and K-IR 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 similar 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 (K-IR) 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 (O-2 saturation similar to 80%). Compared to control, combined inhibition of NO, PGs, Na+/K+-ATPase and K-IR channels (L-NMMA+ketorolac+ouabain+BaCl2; Protocol 1; n=10) blunted the compensatory increase in FBF during HypEx by similar to 50% (29 +/- 6 mL min(-1) vs. 628 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 K-IR 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.