Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of beta-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O-2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 +/- 13.8 beats/min during Cont and similar (17.2 +/- 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 +/- 9.6 and 8.1 +/- 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 +/- 1.9, 1.7 +/- 1.8, and 2.3 +/- 1.2 l/min, respectively, P > 0.4) but larger during Prop (3.4 +/- 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than beta-adrenergic transmission. A potential candidate is beta-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined beta-adrenergic and muscarinic receptor inhibition.
2015. Vol. 308, no 12, H1540-H1546 p.