Hypoxia potentiates exercise-induced sympathetic neural activation in humans

Our purpose was to test the hypothesis that hypoxia potentiates exercise-induced sympathetic neural activation in humans. In 15 young (20-30 yr) healthy subjects, lower leg muscle sympathetic nerve activity (MSNA, peroneal nerve; microneurography), venous plasma norepinephrine (PNE) concentrations, heart rate, and arterial blood pressure were measured at rest and in response to rhythmic handgrip exercise performed during normoxia or isocapnic hypoxia (inspired O₂ concn of 10%). Study I (n = 7): Brief (3-4 min) hypoxia at rest did not alter MSNA, PNE, or arterial pressure but did induce tachycardia [17 ± 3 (SE) beats/min; P < 0.05]. During exercise at 50% of maximum, the increases in MSNA (346 ± 81 vs. 207 ± 14% of control), PNE (175 ± 25 vs. 120 ± 11% of control), and heart rate (36 ± 2 vs. 20 ± 2 beats/min) were greater during hypoxia than during normoxia (P < 0.05), whereas the arterial pressure response was not different (26 ± 4 vs. 25 ± 4 mmHg). The increase in MSNA during hypoxic exercise also was greater than the simple sum of the separate responses to hypoxia and normoxic exercise (P < 0.05). Study II (n = 8): In contrast to study I, during 2 min of exercise (30% max) performed under conditions of circulatory arrest and 2 min of postexercise circulatory arrest (local ischemia), the MSNA and PNE responses were similar during systemic hypoxia and normoxia. Arm ischemia without exercise had no influence on any variable during hypoxia or normoxia. We conclude that 1) hypoxia potentiates exercise-evoked sympathoexcitation in humans, 2) the augmented sympathetic activation may be due to a synergistic interaction between these two stimuli, and 3) the mechanism underlying the greater sympathetic response to hypoxic exercise has its origin in the contracting skeletal muscles.