Human hypoxic ventilatory response with blood dopamine content under intermittent hypoxic training

Abstract

Adaptation to intermittent hypoxia can enhance a hypoxic ventilatory response (HVR) in healthy humans. Naturally occurring oscillations in blood dopamine (DA) level may modulate these responses. We have measured ventilatory response to hypoxia relative to blood DA concentration and its precursor DOPA before and after a 2-week course of intermittent hypoxic training (IHT). Eighteen healthy male subjects (mean 22.8+/-2.1 years old) participated in the study. HVRs to isocapnic, progressive, hypoxic rebreathing were recorded and analyzed using piecewise linear approximation. Rebreathing lasted for 5-6 min until inspired O2 reached 8 to 7%. IHT consisted of three identical daily rebreathing sessions separated by 5-min breaks for 14 consecutive days. Before and after the 2-week course of IHT, blood was sampled from the antecubital vein to measure DA and DOPA content. The investigation associated pretraining high blood DA and DOPA values with low HVR (r = -0.66 and -0.75, respectively), elevated tidal volume (r = 0.58 and 0.37) and vital capacity (r = 0.69 and 0.58), and reduced respiratory frequency (r = -0.89 and -0.82). IHT produced no significant change in ventilatory responses to mild hypoxic challenge (Peto2 from 110 to 70-80 mm Hg; 1 mm Hg = 133.3 Pa) but elicited a 96% increase in ventilatory response to severe hypoxia (from 70-80 to 45 mm Hg). Changes in HVRs were not accompanied by statistically significant shifts in blood DA content (24% change), although a twofold increase in DOPA concentration was observed. Individual subject's changes in DA and DOPA content were not correlated with HVR changes when these two parameters were evaluated in relation to the IHT. We hypothesize that DA flowing to the carotid body through the blood may provoke DA autoreceptor-mediated inhibition of endogenous DA synthesis-release, as shown in our baseline data.

Repeated hypoxic exposures change respiratory chemoreflex control in humans

“…The repeated daily exposures to hypoxia produced a marked enhancement of the initial ventilatory response to hypoxia by the end of the 14 days, a finding similar to that of others using a variety of repeated exposure protocols (Levine et al 1992;Savourey et al 1996;Katayama et al 1998;Serebrovskaya et al 1999;Garcia et al 2000b). We also observed that during each 20 min exposure to hypoxia the ventilatory response declined slowly, again a finding similar to that of others (e.g.…”

“…For the second type, involving daily exposures to hypoxia, several studies in humans have demonstrated that the initial ventilatory response to hypoxia is enhanced (Levine et al 1992;Savourey et al 1996;Katayama et al 1998;Serebrovskaya et al 1999;Garcia et al 2000b). Most of these studies involved subjects spending time in hypobaric chambers at simulated altitudes: 30 min daily for 6 days at 4 500 m (Katayama et al 1998) or 8 h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m (Savourey et al 1996), or 45 min daily for 5 days week _1 for 5 weeks (Levine et al 1992), with the latter complicated by exercise during the exposures.…”

“…Most of these studies involved subjects spending time in hypobaric chambers at simulated altitudes: 30 min daily for 6 days at 4 500 m (Katayama et al 1998) or 8 h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m (Savourey et al 1996), or 45 min daily for 5 days week _1 for 5 weeks (Levine et al 1992), with the latter complicated by exercise during the exposures. However, two studies involved hypoxic exposures at normal barometric pressures, that of Serebrovskaya et al (1999) in subjects exposed to three 5 min bouts of progressive hypoxia daily for 14 consecutive days, and that of Garcia et al (2000a) with 2 h daily exposures to 13 % inspired oxygen for 12 days. Such findings also implicate changes in the peripheral chemoreflex.…”

Chronic Intermittent Hypoxia Elicits Serotonin-Dependent Plasticity in the Central Neural Control of Breathing

“…This effect is similar to results from studies of intermittent hypoxia "training" in human subjects. Serebrovskaya et al (1999) report that three hypoxic episodes (7-8%) of 5-6 min for 14 consecutive days in humans increased the ventilatory response to moderate (increased by 96% at 45 mmHg), but not mild (70 -80 mmHg) hypoxia. Thus, intermittent hypoxia augments both short-term hypoxic ventilatory and phrenic responses, but only during moderate to severe hypoxia.…”

In hamsters the D1 receptor antagonist SCH23390 depresses ventilation during hypoxia

“…Exposure of animals and human beings to hypoxia increases both plasma and brain levels of dopamine [34,43]. Ventilatory responses to hypoxia may be modulated by dopamine acting on dopaminergic receptors divided into D1-like (D1 and D5) and D2-like (D2, D3 and D4) subtypes [28].…”