A universal O₂ sensor presumes that compensation for impaired O₂ delivery is triggered by low O₂ tension, but in humans, comparisons of compensatory responses to altered arterial O₂ content (Ca_O2) or tension (Pa_O2) have not been reported. To directly compare cardiac output (_TOT) and leg blood flow (LBF) responses to a range of Ca_O2 and Pa_O2, seven healthy young men were studied during two-legged knee extension exercise with control hemoglobin concentration ([Hb] = 144.4 ± 4 g/l) and at least 1 wk later after isovolemic hemodilution ([Hb] = 115 ± 2 g/l). On each study day, subjects exercised twice at 30 W and on to voluntary exhaustion with an FI_O2 of 0.21 or 0.11. The interventions resulted in two conditions with matched Ca_O2 but markedly different Pa_O2 (hypoxia and anemia) and two conditions with matched Pa_O2 and different Ca_O2 (hypoxia and anemia + hypoxia). Pa_O2 varied from 46 ± 3 Torr in hypoxia to 95 ± 3 Torr (range 37 to >100) in anemia (P < 0.001), yet LBF at exercise was nearly identical. However, as Ca_O2 dropped from 190 ± 5 ml/l in control to 132 ± 2 ml/l in anemia + hypoxia (P < 0.001), _TOT and LBF at 30 W rose to 12.8 ± 0.8 and 7.2 ± 0.3 l/min, respectively, values 23 and 47% above control (P < 0.01). Thus regulation of _TOT, LBF, and arterial O₂ delivery to contracting intact human skeletal muscle is dependent for signaling primarily on Ca_O2, not Pa_O2. This finding suggests that factors related to Ca_O2 or [Hb] may play an important role in the regulation of blood flow during exercise in humans.

vasodilatation; red blood cell; hemoglobin; anemia; hypoxia; nitric oxide

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