Chronic hypoxia is associated with elevated sympathetic activity and hypertension in patients with chronic pulmonary obstructive disease (Heindl et al. 2001; Imadojemu et al. 2002). However, the effect of chronic hypoxia on systemic and regional sympathetic activity in healthy humans remains unknown. To determine if chronic hypoxia in healthy humans is associated with hyperactivity of the sympathetic nervous system, we measured intra-arterial blood pressure (20-gauge femoral artery catheter), arterial blood gases, systemic and muscular noradrenaline spillover and vascular conductances in nine Danish lowlanders (4 females and 5 males) at sealevel and after 9 weeks of exposure at 5260 m (barometric pressure = 408 mmHg). Their mean (± S.E.M.) age, height and weight were 24.3 ± 0.5 years, 176 ± 3 cm and 74 ± 4 kg, respectively. The subjects were informed about the procedures and risks of the study before giving written informed consent to participate as approved by the Copenhagen-Fredriksberg Ethical Committee. Experiments were performed according to the Declaration of Helsinki. Differences in the measured variables among conditions were assessed with ANOVA for repeated measures, with the sex as a between-subjects factor with two levels. Student’s paired t test was applied when appropriate to determine if the observed differences between the means were significant or not. Significance was accepted at P < 0.05.
Mean blood pressure was 28 % higher at altitude (P < 0.01) due to increases in both systolic (18 % higher, P < 0.05) and diastolic (41 % higher, P < 0.001) blood pressures. Cardiac output (indocyanin green injection) and leg blood flow (thermodilution, femoral vein catheter) were not altered by chronic hypoxia, but systemic vascular conductance was reduced by 30 % (P < 0.05). Plasma arterial noradrenaline (NA) and adrenaline concentration were 3.7- and 2.4-fold higher at altitude, respectively (P < 0.05). The elevation of plasma arterial NA concentration was caused by a 3.8-fold higher whole-body noradrenaline release (P < 0.001) since whole-body noradrenaline clearance was similar in both conditions. Leg NE spillover was increased similarly ( X 3.2, P < 0.05). These changes occurred despite systemic O2 delivery being greater after altitude acclimatisation than at sea level, due to 37 % higher blood haemoglobin concentration.
In summary, this study shows that chronic hypoxia causes increased systemic arterial pressure and massive activation of the sympathetic nervous system in healthy humans, despite improved oxygenation with acclimatisation. Strikingly, sympathetic activation reaches levels similar to those observed in chronic heart failure patients (Kaye et al. 1995). It is particularly important to establish the functional and pathophysiological consequences that may be derived from the chronic hypoxia induced sympathetic hyperactivity.
Special thanks are given to Harriet Wagner, Carsten Nielsen, Karin Hansen and Birgitte Jessen for their excellent technical assistance. This study was supported by a grant from The Danish National Research Foundation (504-14).