Carotid chemoreceptor control of muscle sympathetic nerve activity in hypobaric hypoxia

What is the central question of this study? High-altitude hypoxia increases muscle sympathetic nerve activity (MSNA), but whether intravenous infusion of dopamine, to blunt the responsiveness of the carotid chemoreceptors, reduces MSNA at high altitude is not known. What is the main finding and its importance? Muscle sympathetic nerve activity was elevated after 15-17 days of high-altitude hypoxia (3454 m) compared with values at 'sea level' (432 m). However, intravenous dopamine infusion to blunt the responsiveness of the carotid chemoreceptors did not significantly decrease MSNA either at sea level or at high altitude, suggesting that high-altitude sympathoexcitation arises via a different mechanism. High-altitude hypoxia causes pronounced sympathoexcitation, but the underlying mechanisms remain unclear. We tested the hypothesis that i.v. infusion of dopamine to attenuate carotid chemoreceptor responsiveness would reduce muscle sympathetic nerve activity (MSNA) at high altitude. Nine healthy individuals [mean (SD); 26 (4) years of age] were studied at 'sea level' (SL; Zurich) and at high altitude (ALT; 3454 m; 15-17 days after arrival), both while breathing the ambient air and during an acute incremental hypoxia test (eight 3 min stages; partial pressure of end-tidal O₂ 90-45 mmHg). Intravenous infusions of dopamine (3 microg kg^-1  min^-1 ) and placebo (saline) were administered on both study days, according to a single-blind randomized cross-over design. Sojourn to high altitude decreased the partial pressure of end-tidal O₂ (to ∼60 mmHg) and increased minute ventilation [V̇E; mean ± SEM, SL versus ALT: saline, 8.6 ± 0.5 versus 11.3 ± 0.6 l min^-1 ; dopamine, 8.2 ± 0.5 versus 10.6 ± 0.8 l min^-1 ; P < 0.05] and MSNA burst frequency by ∼80% [SL versus ALT: saline, 16 ± 3 versus 28 ± 4 bursts min^-1 ; dopamine, 16 ± 4 versus 31 ± 4 bursts min^-1 ; P < 0.05) when breathing the ambient air, but were not different with dopamine. Increases in MSNA burst frequency and V̇E during the acute incremental hypoxia test were greater at ALT than SL (P < 0.05). Dopamine did not affect the magnitude of the MSNA burst frequency response to acute incremental hypoxia at either SL or ALT. However, V̇E was lower with dopamine than saline administration throughout the acute incremental hypoxia test at ALT. These data indicate that i.v. infusion of low-dose dopamine to blunt the responsiveness of the carotid chemoreceptors does not significantly decrease MSNA at high altitude.