Changes in autonomic response and resistance to acute graded hypoxia during intermittent hypoxic training

A placebo-controlled study was performed to examine the effects of intermittent normobaric hypoxic preconditioning on the autonomic regulation of blood flow, as well as on heart rate variability (HRV) response and resistance to acute hypoxia, in healthy male volunteers. Intermittent hypoxic training (IHT) increased the efficiency of the mechanisms of autonomic regulation of heart rate (HR) at rest by increasing the parasympathetic control and optimized changes in HRV during simulated acute hypoxia. The hypoxic preconditioning contributed to increased resistance of the body to simulated acute hypoxia, as reflected by less marked hemoglobin desaturation and a smaller increase in the HR. The training effects of the IHT were more pronounced in the subjects with an initially low resistance to a hypoxic factor as compared to those resistant to acute hypoxia.     

Time domains of the hypoxic ventilatory response in ectothermic vertebrates

Over a decade has passed since Powell et al. (Respir Physiol 112:123–134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however, have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure). To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response) and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123–134, 1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O₂ supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed here, it is noted that this area has received little attention. We attempt to redefine time domains in a more ‘holistic’ fashion that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains in mind.     

Human skeletal muscle fiber type alteration with high-intensity intermittent training

The response of muscle fiber type proportions and fiber areas to 15 weeks of strenuous high-intensity intermittent training was investigated in twenty-four carefully ascertained sedentary (14 women and 10 men) and 10 control (4 women and 6 men) subjects. The supervised training program consisted mainly of series of supramaximal exercise lasting 15 s to 90 s on a cycle ergometer. Proportions of muscle fiber type and areas of the fibers were determined from a biopsy of the vastus lateralis before and after the training program. No significant change was observed for any of the histochemical characteristics in the control group. Training significantly increased the proportion of type I and decreased type IIb fibers, the proportion of type IIa remained unchanged. Areas of type I and IIb fibers increased significantly with training. These results suggest that high-intensity intermittent training in humans may alter the proportion of type I and the area of type I and IIb fibers and in consequence that fiber type composition in human vastus lateralis muscle is not determined solely by genetic factors.     

Living high-training low increases hypoxic ventilatory response of well-trained endurance athletes.

This study determined whether "living high-training low" (LHTL)-simulated altitude exposure increased the hypoxic ventilatory response (HVR) in well-trained endurance athletes. Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxic exposure (LHTLc, n = 12), 20 nights of intermittent hypoxic exposure (four 5-night blocks of hypoxia, each interspersed with 2 nights of normoxia, LHTLi, n = 10), or control (Con, n = 11). LHTLc and LHTLi slept 8-10 h/day overnight in normobaric hypoxia (approximately 2,650 m); Con slept under ambient conditions (600 m). Resting, isocapnic HVR (DeltaVE/DeltaSp(O(2)), where VE is minute ventilation and Sp(O(2)) is blood O(2) saturation) was measured in normoxia before hypoxia (Pre), after 1, 3, 10, and 15 nights of exposure (N1, N3, N10, and N15, respectively), and 2 nights after the exposure night 20 (Post). Before each HVR test, end-tidal PCO(2) (PET(CO(2))) and VE were measured during room air breathing at rest. HVR (l. min(-1). %(-1)) was higher (P < 0.05) in LHTLc than in Con at N1 (0.56 +/- 0.32 vs. 0.28 +/- 0.16), N3 (0.69 +/- 0.30 vs. 0.36 +/- 0.24), N10 (0.79 +/- 0.36 vs. 0.34 +/- 0.14), N15 (1.00 +/- 0.38 vs. 0.36 +/- 0.23), and Post (0.79 +/- 0.37 vs. 0.36 +/- 0.26). HVR at N15 was higher (P < 0.05) in LHTLi (0.67 +/- 0.33) than in Con and in LHTLc than in LHTLi. PET(CO(2)) was depressed in LHTLc and LHTLi compared with Con at all points after hypoxia (P < 0.05). No significant differences were observed for VE at any point. We conclude that LHTL increases HVR in endurance athletes in a time-dependent manner and decreases PET(CO(2)) in normoxia, without change in VE. Thus endurance athletes sleeping in mild hypoxia may experience changes to the respiratory control system.     

Adaptive changes in hypercapnic ventilatory response during training and detraining

To confirm the effects of physical training and detraining on CO2 chemosensitivity, we followed hypercapnic ventilatory response at rest in the same five subjects during pre-, post- and detraining for 6 years. They joined our university badminton teams as freshmen and participated regularly in their team's training for about 3 h a day, three times a week, for 4 years. After that they retired from their teams and stopped training in order to study in the graduate school for 2 years. Maximum pulmonary ventilation (VEmax) and maximal oxygen uptake (VO2max) for each subject were determined during maximal treadmill exercise. The slope (S) of ventilatory response to carbon dioxide at rest was measured by Read's rebreathing method. Mean values of VEmax increased statistically during training and decreased statistically during detraining. A similar tendency was observed in VO2max. The average value of S before training was 1.91 l.min-1.mmHg-1, (+/- ) SD 0.52 and it decreased gradually with increasing training periods; the difference between the S values before (1980) and after training (1982, 1983 and 1984) were all significant. Furthermore, the mean values of S increased significantly during detraining as compared with those obtained at the end of training (April 1984). We concluded that in normal subjects, long-term physical training increases aerobic work capacity and decreases CO2 ventilatory responsiveness, and that the ventilatory adaptations with training observed here are reversible through detraining.     

The acute hypoxic ventilatory response: testing the adaptive significance in human populations

The acute Hypoxic Ventilatory Response (HVR) is an important component of human hypoxia tolerance, hence presumably physiological adaptation to high altitude. We measured the isocapnic HVR (L min(-1) %(-1)) in two genetically divergent low altitude southern African populations. The HVR does not differ between African Xhosas (X) and Caucasians (C) (X:-0.34+/-0.36; C:-0.42+/-0.33; P > 0.34), but breathing patterns do. Among all Xhosa subjects, size-independent tidal volume was smaller (X: 0.75+/-0.20; C: 1.11+/-0.32 L; P < 0.01), breathing frequency higher (X: 22.2+/-5.7; C: 14.3+/-4.2 breaths min(-1); P < 0.01) and hypoxic oxygen saturation lower than among Caucasians (X: 78.4+/-4.7%; C: 81.7+/-4.7%; P < 0.05). The results remained significant if subjects from Xhosa and Caucasian groups were matched for gender, body mass index and menstrual cycle phase in the case of females. The latter also employed distinct breathing patterns between populations in normoxia. High repeatability (intra-class correlation coefficient) of the HVR in both populations (0.77-0.87) demonstrates that one of the prerequisites for natural selection, consistent between-individual variation, is met. Finally, we explore possible relationships between inter-population genetic distances and HVR differences among Xhosa, European, Aymara Amerindians, Tibetan and Chinese populations. Inter-population differences in the HVR are not attributable to genetic distance (Mantel Z-test, P = 0.59). The results of this study add novel support for the hypothesis that differences in the HVR, should they be found between other human populations, may reflect adaptation to hypoxia rather than genetic divergence through time.     

Microcirculation characteristics in apparently healthy subjects during acute hypoxia and intermittent hypoxic training

The characteristics of the microcirculation in the forearm skin of 29 apparently healthy male volunteers were studied in acute hypoxia and during intermittent hypoxic training (IHT) using computer laser Doppler flowmetry. It was shown that short-term exposure of apparently healthy subjects to simulated acute hypoxia optimized the microcirculation owing to sympathetic innervation and concomitant rearrangement of microvascular tone regulation (activation of skin perfusion and reduction of blood flow through arteriovenular shunts when the neurogenic tone component increases). A second (placebo-controlled) series of experiments showed that long-term hypoxic preconditioning (20 IHT sessions) facilitated fixing of the adaptive dynamic rearrangements aimed at microcirculation improvement. The microvasculature response during acute hypoxia and a course of IHT depends on the initial sensitivity of subjects to simulated hypoxia. Significant perfusion enhancement in the tissues studied and microvascular tone normalization were observed in the subjects that were initially sensitive to hypoxia.     

Acute lung injury augments hypoxic ventilatory response in the absence of systemic hypoxemia.

The objective of the present study was to examine the impact of early stages of lung injury on ventilatory control by hypoxia and hypercapnia. Lung injury was induced with intratracheal instillation of bleomycin (BM; 1 unit) in adult, male Sprague-Dawley rats. Control animals underwent sham surgery with saline instillation. Five days after the injections, lung injury was present in BM-treated animals as evidenced by increased neutrophils and protein levels in bronchoalveolar lavage fluid, as well as by changes in lung histology and computed tomography images. There was no evidence of pulmonary fibrosis, as indicated by lung collagen content. Basal core body temperature, arterial Po(2), and arterial Pco(2) were comparable between both groups of animals. Ventilatory responses to hypoxia (12% O(2)) and hypercapnia (7% CO(2)) were measured by whole body plethysmography in unanesthetized animals. Baseline respiratory rate and the hypoxic ventilatory response were significantly higher in BM-injected compared with control animals (P = 0.003), whereas hypercapnic ventilatory response was not statistically different. In anesthetized, spontaneously breathing animals, response to brief hyperoxia (Dejours' test, an index of peripheral chemoreceptor sensitivity) and neural hypoxic ventilatory response were augmented in BM-exposed relative to control animals, as measured by diaphragmatic electromyelograms. The enhanced hypoxic sensitivity persisted following bilateral vagotomy, but was abolished by bilateral carotid sinus nerve transection. These data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in early lung injury in the absence of pulmonary fibrosis and arterial hypoxemia.     

Time under tension and blood lactate response during four different resistance training methods

Mechanical stimuli have often been suggested to be the major determinant of resistance training adaptations; however, some studies suggested that metabolic changes also play an important role in the gains of muscle size and strength. Several resistance training methods (RTM) have been employed with the purpose of manipulating mechanical and metabolic stimuli; however, information about their physiological effects are scarce. The objective of this study was to compare the time under tension (TUT) and blood lactate responses among four different RTM reported in the literature. The four RTM were performed in a knee extension machine at 10 repetition maximum (RM) load by 12 recreationally trained young men. The RTM tested were: 10RM, super-slow (SL-subjects performed one 60-second repetition with 30 seconds for eccentric and 30 seconds for concentric phase), functional isometrics (FI-in each repetition, a five-second maximal isometric contraction was executed with the knees fully extended) and adapted vascular occlusion (VO-subjects performed a 20-second maximal isometric contraction with the knees fully extended and immediately proceeded to normal isoinertial lifts). According to the results, all RTM produced significant increases in blood lactate levels. However, blood lactate responses during FI (4.48+/-1.57 mM) and VO (4.23+/-1.66 mM) methods were higher than the SL method (3.41+/-1.14 mM). The TUT for SL (60 s), FI (56.33+/-6.46 s), and VO (53.08+/-4.76 s) methods were higher than TUT for 10RM (42.08+/-3.18 s). Additionally, TUT for the SL method was higher than TUT during the VO method. Therefore, the SL method may not be recommended if one wants to provide a high metabolic stimulus. The FI method appeared to be especially effective in promoting both type of stimuli.     

Brainstem activation of platelet-derived growth factor-beta receptor modulates the late phase of the hypoxic ventilatory response

The early phase of the biphasic ventilatory response to hypoxia in mammals is critically dependent on NMDA glutamate receptor activation within the nucleus of the solitary tract. However, the mechanisms underlying the subsequent development of the typical ventilatory roll-off are unclear and could underlie important roles in the functional and molecular adaptation to oxygen deprivation. Because the growth factor platelet-derived growth factor (PDGF)-BB can modulate the open channel probability of NMDA receptors by activating PDGF-beta receptors, its contribution to hypoxic ventilatory roll-off was examined. Administration of PDGF-BB, but not PDGF-AA, in the nucleus of the solitary tract was associated with significant attenuations of the early hypoxic ventilatory response in conscious rats. Furthermore, marked reductions in the magnitude of hypoxic ventilatory roll-off occurred in mice heterozygous for a mutation in the PDGF-beta receptor. Administration of a PDGF-beta receptor antagonist to wild-type littermates elicited similar declines in hypoxic ventilatory roll-off. The relative abundance of PDGF-beta receptors was confirmed in the nucleus of the solitary tract and other nuclei implicated in the hypoxic ventilatory response. In nucleus of the solitary tract lysates, PDGF-beta receptor tyrosine phosphorylation was temporally correlated with hypoxic ventilatory roll-off formation. Increased PDGF-B chain mRNA expression was induced by hypoxia in the nucleus of the solitary tract, and PDGF-B chain immunoreactivity colocalized with approximately 40% of nucleus of the solitary tract neurons, demonstrating hypoxia-induced c-Fos enhancements. Thus, PDGF-BB release and PDGF-beta receptor activation in the nucleus of the solitary tract are critical components of hypoxic ventilatory roll-off and may have important functional implications in processes underlying survival and acclimatization to hypoxic environments.     

Effects of chronic hypoxia on MK-801-induced changes in the acute hypoxic ventilatory response.

Chronic hypoxia increases the sensitivity of the central nervous system to afferent input from carotid body chemoreceptors. We hypothesized that this process involves N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms and predicted that chronic hypoxia would change the effect of the NMDA receptor blocker dizocilpine (MK-801) on the poikilocapnic hypoxic ventilatory response (HVR). Male Sprague-Dawley rats were studied before and after acclimatization to hypoxia (70 Torr inspiratory Po(2) for 9 days). We measured ventilation (VI) and the HVR before and after systemic MK-801 treatment (3 mg/kg ip). MK-801 resulted in a constant respiratory frequency (approximately 175 min(-1)) during acute exposure to 10% and 30% O(2) before and after acclimatization. MK-801 had no effect on tidal volume (VT) before acclimatization, but it significantly decreased Vt when the animals were breathing 10% O(2) after acclimatization. The net effect of MK-801 was to eliminate the O(2) sensitivity of Vi before (via changes in respiratory frequency) and after (via changes in VT) acclimatization. Hence, chronic hypoxia altered the effect of MK-801 on the acute HVR, primarily because of increased effects on Vt. This indicates that changes in NMDA receptor-mediated neurotransmission may be involved in ventilatory acclimatization to hypoxia. However, further experiments are necessary to determine the precise location of such plasticity in the central nervous system.     

Selected contribution: variation in acute hypoxic ventilatory response is linked to mouse chromosome 9.

Genetic determinants confer variation among inbred mouse strains with respect to the magnitude and pattern of breathing during acute hypoxic challenge. Specifically, inheritance patterns derived from C3H/HeJ (C3) and C57BL/6J (B6) parental strains suggest that differences in hypoxic ventilatory response (HVR) are controlled by as few as two genes. The present study demonstrates that at least one genetic determinant is located on mouse chromosome 9. This genotype-phenotype association was established by phenotyping 52 B6C3F2 (F2) offspring for HVR characteristics. A genome-wide screen was performed using microsatellite DNA markers (n = 176) polymorphic between C3 and B6 mice. By computing log-likelihood values (LOD scores), linkage analysis compared marker genotypes with minute ventilation (&Vdot;E), tidal volume (VT), and mean inspiratory flow (VT/TI, where TI is inspiratory time) during acute hypoxic challenge (inspired O2 fraction = 0.10, inspired CO2 fraction = 0.03 in N2). A putative quantitative trait locus (QTL) positioned in the vicinity of D9Mit207 was significantly associated with hypoxic VE (LOD = 4.5), VT (LOD = 4.0), and VT/TI (LOD = 5.1). For each of the three HVR characteristics, the putative QTL explained more than 30% of the phenotypic variation among F(2) offspring. In conclusion, this genetic model of differential HVR characteristics demonstrates that a locus approximately 33 centimorgans from the centromere on mouse chromosome 9 confers a substantial proportion of the variance in VE, VT, and VT/TI during acute hypoxic challenge.     

Effects of aging and training status on ventilatory response during incremental cycling exercise

The aim of this study was to examine the effect of aging and training status on ventilatory response during incremental cycling exercise. Eight young (24 ± 5 years) and 8 older (64 ± 3 years) competitive cyclists together with 8 young (27 ± 4 years) and 8 older (63 ± 2 years) untrained individuals underwent a continuous incremental cycling test to exhaustion to determine ventilatory threshold (VT), respiratory compensation point (RCP), and maximal oxygen uptake (VO?max). In addition, the isocapnic buffering (IB) phase was calculated together with the hypocapnic hyperventilation. Ventilatory threshold occurred at similar relative exercise intensities in all groups, whereas RCP was recorded at higher intensities in young and older cyclists compared to the untrained subjects. The IB phase, reported as the difference between VT and RCP and expressed either in absolute (ml·min?1·kg?1 VO?) or in relative terms, was greater (p < 0.01) in both young and older trained cyclists than in untrained subjects, who were also characterized by a lower exercise capacity. Isocapnic buffering was particularly small in the older untrained volunteers. Although young untrained and older trained subjects had a similar level of VO?max, older athletes exhibited a larger IB. In addition, a higher absolute but similar relative IB was observed in young vs. older cyclists, despite a higher VO?max in the former. In conclusion, the present study shows that aging is associated with a reduction of the IB phase recorded during an incremental exercise test. Moreover, endurance training induces adaptations that result in an enlargement of the IB phase independent of age. This information can be used for the characterization and monitoring of the physiological adaptations induced by endurance training.     

慢性间断低氧大鼠体重和血糖变化与埃他卡林的干预效应

目的:探讨慢性低氧对大鼠体重和血糖的影响及埃他卡林的作用。方法:将埃他卡林治疗组和低氧组大鼠置于常压低氧舱中建立模型,然后测血糖,测量大鼠体重,计算体重增加率。结果:慢性低氧大鼠体重增长最低,同时血糖较正常组显著下降;埃他卡林治疗的低氧大鼠体重显著升高,血糖与正常组接近。结论:埃他卡林可以促进低氧大鼠体重增加,稳定血糖,改善低氧大鼠营养状况。     

Neurotransmitter mechanisms in the enhancement of the hypoxic ventilatory response by antecedent hyperoxia in the anesthetized rat.

A brief period of antecedent oxygen breathing enhances the ventilatory response to hypoxia. The mechanisms of this phenomenon are uncertain and have been variably linked to the central glutamatergic or nitrergic pathways. In the present study we put a question of how blockade of either neurotransmitter pathway would compare with the concurrent blockade of them both in terms of the enhancement of posthyperoxic hypoxic ventilation. The study was performed on the anesthetized, vagotomized, spontaneously breathing rats divided into the following experimental groups: control NaCl-treated, glutamate blocker 2-amino-5-phosphonopentanoic acid (AP5)-treated, nitric oxide synthase blocker 7-nitroindazol (7NI)-treated, and AP5+7NI-treated. The protocol consisted of measuring the ventilatory response to 12% O2, a steady- state poikilocapnic hypoxia, undertaken in three consecutive conditions in each animal: the initial control, 25 min after injection of a given chemical agent, and then after a 15-min period of oxygen breathing. Respiration was evaluated from the diaphragmatic EMG signal. We found that the posthyperoxic hypoxic ventilatory enhancement was but partially dampened by either AP5 or 7NI. Concurrent administration of the two blockers further diminished, but did not abolish, the hypoxic ventilatory enhancement. We conclude that although the glutamate-NO system accounts for an appreciable part of the posthyperoxic hypoxic ventilatory enhancement, other, as yet unclear, mechanisms contribute as well. These mechanisms may be worth exploring given the substantial enhancing effect the antecedent oxygen has on hypoxic hyperventilation.     

Effects of intermittent hypoxic training on amino and fatty acid oxidative combustion in human permeabilized muscle fibers.

The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions ( approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2 ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08 mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max), and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.     

Performance of runners and swimmers after four weeks of intermittent hypobaric hypoxic exposure plus sea level training.

This double-blind, randomized, placebo-controlled trial examined the effects of 4 wk of resting exposure to intermittent hypobaric hypoxia (IHE, 3 h/day, 5 days/wk at 4,000-5,500 m) or normoxia combined with training at sea level on performance and maximal oxygen transport in athletes. Twenty-three trained swimmers and runners completed duplicate baseline time trials (100/400-m swims, or 3-km run) and measures for maximal oxygen uptake (VO(2max)), ventilation (VE(max)), and heart rate (HR(max)) and the oxygen uptake at the ventilatory threshold (VO(2) at VT) during incremental treadmill or swimming flume tests. Subjects were matched for sex, sport, performance, and training status and divided randomly between hypobaric hypoxia (Hypo, n = 11) and normobaric normoxia (Norm, n = 12) groups. All tests were repeated within the first (Post1) and third weeks (Post2) after the intervention. Time-trial performance did not improve in either group. We could not detect a significant difference between groups for a change in VO(2max), VE(max), HR(max), or VO(2) at VT after the intervention (group x test interaction P = 0.31, 0.24, 0.26, and 0.12, respectively). When runners and swimmers were considered separately, Hypo swimmers appeared to increase VO(2max) (+6.2%, interaction P = 0.07) at Post2 following a precompetition taper and increased VO(2) at VT (+8.9 and +12.1%, interaction P = 0.007 and 0.006, at Post1 and Post2). We conclude that this "dose" of IHE was not sufficient to improve performance or oxygen transport in this heterogeneous group of athletes. Whether there are potential benefits of this regimen for specific sports or training/tapering strategies may require further study.     

The effects of intermittent exposure to hypoxia during endurance exercise training on the ventilatory responses to hypoxia and hypercapnia in humans

The present study was performed to investigate the effects of a combination of intermittent exposure to hypoxia during exercise training for short periods on ventilatory responses to hypoxia and hypercapnia (HVR and HCVR respectively) in humans. In a hypobaric chamber at a simulated altitude of 4,500 m (barometric pressure 432 mmHg), seven subjects (training group) performed exercise training for 6 consecutive days (30 min · day⁻¹), while six subjects (control group) were inactive during the same period. The HVR, HCVR and maximal oxygen uptake (V˙O_{2 max}) for each subject were measured at sea level before (pre) and after exposure to intermittent hypoxia. The post exposure test was carried out twice, i.e. on the 1st day and 1 week post exposure. It was found that HVR, as an index of peripheral chemosensitivity to hypoxia, was increased significantly (P < 0.05) in the control group after intermittent exposure to hypoxia. In contrast, there was no significant increase in HVR in the training group after exposure. The HCVR in both groups was not changed by intermittent exposure to hypoxia, while V˙O_{2 max} increased significantly in the training group. These results would suggest that endurance training during intermittent exposure to hypoxia depresses the increment of chemosensitivity to hypoxia, and that intermittent exposure to hypoxia in the presence or absence of exercise training does not induce an increase in the chemosensitivity to hypercapnia in humans. Accepted: 18 March 1998