A universal O-2 sensor presumes that compensation for impaired O-2 delivery is triggered by low O-2 tension, but in humans, comparisons of compensatory responses to altered arterial O-2 content (Ca-O2) or tension (Pa-O2) have not been reported. To directly compare cardiac output ((Q) over dot(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 FIO2 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 32 +/- 2 ml/l in anemia + hypoxia (P < 0.001), (Q) over dot(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 (Q) over dot(TOT), LBF, and arterial O-2 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.
