Naloxone does not affect ventillatory responses to hypoxia and hypercapnia in rats

Ventilatory responses (tidal volume, respiratory frequency, and minute ventilation) to steady-state hypoxia and steady-state hypercapnia were measured plethysmographically in awake unrestrained adult rats, before and after subcutaneous injection of placebo (saline) or naloxone in doses up to 5.0 mg/kg. Naloxone did not alter the ventilatory responses to hypoxia or hypercapnia.     

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     

Human ventilatory responsiveness to hypoxia is unrelated to maximal aerobic capacity.

Ventilatory responsiveness to hypoxia (HVR) has been reported to be different between highly trained endurance athletes and healthy sedentary controls. However, a linkage between aerobic capacity and HVR has not been a universal finding. The purpose of this study was to examine the relationship between HVR and maximal oxygen consumption (VO2 max) in healthy men with a wide range of aerobic capacities. Subjects performed a HVR test followed by an incremental cycle test to exhaustion. Participants were classified according to their maximal aerobic capacity. Those with a VO2 max of >or=60 ml x kg(-1) x min(-1) were considered highly trained (n = 13); those with a VO2 max of 50-60 ml x kg(-1) x min(-1) were considered moderately-trained (n = 18); and those with a VO2 max of <50 ml x kg(-1) x min(-1) were considered untrained (n = 24). No statistical differences were detected between the three groups for HVR (P > 0.05), and the HVR values were variable within each group (range: untrained = 0.28-1.61, moderately trained = 0.23-2.39, and highly trained = 0.08-1.73 l x min.%arterial O2 saturation(-1)). The relationship between HVR and VO2 max was not statistically significant (r = -0.1723; P > 0.05). HVR was also unrelated to maximal minute ventilation and ventilatory equivalents for O2 and CO2. We found that a spectrum of hypoxic ventilatory control is present in well-trained endurance athletes and moderately and untrained men. We interpret these observations to mean that other factors are more important in determining hypoxic ventilatory control than physical conditioning per se.     

ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats

We reported previously that intermittent hypoxia with CO(2) to maintain eucapnia (IH-C) elevates plasma endothelin-1 (ET-1) and arterial pressure. In small mesenteric arteries (sMA; inner diameter = 150 microm), IH-C augments ET-1 constrictor sensitivity but diminishes ET-1-induced increases in intracellular Ca(2+) concentration, suggesting IH-C exposure increases both ET-1 levels and ET-1-stimulated Ca(2+) sensitization. Because Rho-associated kinase (ROK) can mediate Ca(2+) sensitization, we hypothesized that augmented vasoconstrictor sensitivity to ET-1 in arteries from IH-C-exposed rats is dependent on ROK activation. In thoracic aortic rings, ET-1 contraction was not different between groups, but ROK inhibition (Y-27632, 3 and 10 microM) attenuated ET-1 contraction more in IH-C than in sham arteries (50 +/- 11 and 78 +/- 7% vs. 41 +/- 12 and 48 +/- 9% inhibition, respectively). Therefore, ROK appears to contribute more to ET-1 contraction in IH-C than in sham aorta. In sMA, ROK inhibitors did not affect ET-1-mediated constriction in sham arteries and only modestly inhibited it in IH-C arteries. In ionomycin-permeabilized sMA with intracellular Ca(2+) concentration held at basal levels, Y-27632 did not affect ET-1-mediated constriction in either IH-C or sham sMA and ET-1 did not stimulate ROK translocation. In contrast, inhibition of myosin light-chain kinase (ML-9, 100 microM) prevented ET-1-mediated constriction in sMA from both groups. Therefore, IH-C exposure increases ET-1 vasoconstrictor sensitivity in sMA but not in aorta. Furthermore, ET-1 constriction is myosin light-chain kinase dependent and mediated by Ca(2+) sensitization that is independent of ROK activation in sMA but not aorta. Thus ET-1-mediated signaling in aorta and sMA is altered by IH-C but is dependent on different second messenger systems in small vs. large arteries.     

The ventilatory responses of the caecilian Typhlonectes natans to hypoxia and hypercapnia

Typhlonectes natans empty their lungs in a single extended exhalation and subsequently fill their lungs by using a series of 10-20 inspiratory buccal oscillations. These animals always use this breathing pattern, which effectively separates inspiratory and expiratory airflows, unlike most urodele and anuran amphibians that may use one to many buccal oscillations for lung inflation and typically mix expired and inspired gases. Aquatic hypoxia had no significant effect on the breathing pattern or mechanics in these animals. Aerial hypoxia stimulated ventilatory frequency and increased the number of inspiratory oscillations but had little effect on inspiratory and expiratory tidal volume. Aquatic hypercapnia elicited a large significant increase in air-breathing frequency and minute ventilation compared to the small stimulation of minute ventilation seen during aerial hypercapnia. Some animals responded to aquatic hypercapnia with a series of three or four closely spaced breaths separated by long nonventilatory periods. Overall, T. natans showed little capacity to modulate expiratory or inspiratory tidal volumes and depended heavily on changing air-breathing frequency to meet hypoxic and hypercapnic challenges. These responses are different from those of anurans or urodeles studied to date, which modulate both the number of ventilatory oscillations in lung-inflation cycles and the degree of lung inflation when challenged with peripheral or central chemoreceptor stimulation.     

Effect of intermittent chronic exposure to hypoxia on feeding behaviour of rats

Healthy albino male rats were exposed to a simulated high altitude (HA) equivalent to 25000 ft (7620 m) for 6 h daily, continuously for 21 days to study the feeding behaviour. The 24-h food and water intake and body weight once in 3 days were recorded. Blood samples were drawn once a week from the retro-orbital venous plexus for blood sugar analysis. All the parameters were recorded before, during and after exposure to simulated HA. The results show a decrease in 24-h food and water intake and decreased gain in body weight during hypoxic exposure, which showed a tendency to come back to control during the post-exposure period. The blood sugar reflected a state of mild hyperglycaemia during exposure to HA.     

Chronic intermittent hypoxia reduces ventilatory long-term facilitation and enhances apnea frequency in newborn rats

Ventilatory long-term facilitation (LTF; defined as gradual increase of minute ventilation following repeated hypoxic exposures) is well described in adult mammals and is hypothesized to be a protective mechanism against apnea. In newborns, LTF is absent during the first postnatal days, but its precise developmental pattern is unknown. Accordingly, this study describes this pattern of postnatal development. Additionally, we tested the hypothesis that chronic intermittent hypoxia (CIH) from birth alters this development. LTF was estimated in vivo using whole body plethysmography by exposing rat pups at postnatal days 1, 4, and 10 (P1, P4, and P10) to 10 brief hypoxic cycles (nadir 5% O2) and respiratory recordings during the following 2 h (recovery, 21% O2). Under these conditions, ventilatory LTF (gradual increase of minute ventilation during recovery) was clearly expressed in P10 rats but not in P1 and P4. In a second series of experiments, rat pups were exposed to CIH during the first 10 postnatal days (6 brief cyclic exposures at 5% O2 every 6 min followed by 1 h under normoxia, 24 h a day). Compared with P10 control rats, CIH enhanced hypoxic ventilatory response (estimated during the hypoxic cycles) specifically in male rat pups. Ventilatory LTF was drastically reduced in P10 rats exposed to CIH, which was associated with higher apnea frequency during recovery. We conclude that CIH from birth enhances hypoxic chemoreflex and disrupts LTF development, thus likely contributing to increase apnea frequency.     

Biphasic ventilatory response to hypoxia in unanesthetized rats

To determine the role of postinspiratory inspiratory activity of the diaphragm in the biphasic ventilatory response to hypoxia in unanesthetized rats, we examined diaphragmatic activity at its peak (DI), at the end of expiration (DE), and ventilation in adult unanesthetized rats during poikilocapnic hypoxia (10 % O2) sustained for 20 min. Hypoxia induced an initial increase in ventilation followed by a consistent decline. Tidal volume (VT), frequency of breathing (fR), DI and DE at first increased, then VT and DE decreased, while fR and DI remained enhanced. Phasic activation of the diaphragm (DI-DE) increased significantly at 10, 15 and 20 min of hypoxia. These results indicate that 1) the ventilatory response of unanesthetized rats to sustained hypoxia has a typical biphasic character and 2) the increased end-expiratory activity of the diaphragm limits its phasic inspiratory activation, but this increase cannot explain the secondary decline in tidal volume and ventilation.     

Differences in ventilatory responses to hypoxia and hypercapnia between normal and judo athletes with moderate obesity

Hypercapnic and hypoxic ventilatory sensitivities were compared in twenty-one judoists and 24 control subjects with similar degrees of moderate obesity. Data from ten non-obese control subjects were also included as a reference. Mean body weight (BW) and % of ideal body weight in the judoists and the obese and non-obese controls were 100 +/- 14.8, 94.4 +/- 5.3 and 63.4 +/- 6.1 (mean +/- SD) kg, and 142.3 +/- 16.7, 142.2 +/- 12.9 and 98.4 +/- 10.7%, respectively. Mean body fat in the judoists was 16.2 +/- 13.9%, being 25.3 +/- 7.7% in the obese control group, the difference being significant (p less than 0.01). Hypercapnic sensitivities in terms of the CO2 ventilatory response slope (S) and its normalized value for 70 kg BW (SN) of the obese controls were higher than the judoists. These findings were also verified by the CO2-occlusion pressure responses. S and SN in the obese controls were significantly correlated with BW and % body fat. However, no positive correlation was found between BW and S or SN in the judoists as well as between lean body mass and S or SN in the obese control. Hypoxic sensitivity in terms of the PETO2-ventilation hyperbola slope (A) and its normalized value (AN) in the obese control was significantly higher than the non-obese control, but the difference from the judoists was not significant. A and AN were found to increase with increasing % body fat in both judoists and obese controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Larval starvation reduces responsiveness to feeding stimuli and does not affect feeding preferences in a butterfly

It is commonly assumed that holometabolic insects such as Lepidoptera rely primarily on larval storage reserves for reproduction. Recent studies though have documented a prominent role of adult-derived carbohydrates for butterfly reproduction. Moreover, a few studies have shown that adult butterflies may also benefit from adult-derived amino acids, at least when larval storage reserves are reduced. Given that in holometabolous insects larval deficiencies are carried over into the adult stage, reduced storage reserves have the potential to modulate adult feeding preferences and responses in order to allow for a successful compensation. We tested this hypothesis here in the fruit-feeding butterfly Bicyclus anynana using larval food stress to manipulate storage reserves. Alcohols (methanol, ethanol, butanol, propanol), sugars (maltose, glucose, fructose, sucrose), and acetic acid acted as feeding stimuli, while butterflies did not respond to other substances such as amino acids, yeast, salts, or vitamins. Contrary to expectations, stressed butterflies showed a weaker response than controls to several feeding stimuli. In preference tests, butterflies preferred sugar solutions containing proline, arginine, glutamic acid, acetic acid, or ethanol over plain sugar solutions, but discriminated against salts. However, there were no general differences among starved and control butterflies. We conclude that larval food-stress does not elicit compensatory feeding behavior such as a stronger preference for amino acids or other essential nutrients in B. anynana. Instead, the stress imposed by a period of starvation yielded negative effects.     

Impact of repeated daily exposure to intermittent hypoxia and mild sustained hypercapnia on apnea severity

We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (ΔPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 ± 0.42 fraction of baseline, P ≤ 0.01, vs. day 10: 1.53 ± 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, ΔPes and tidal volume measures were greater on day 1 and 10 compared with baseline (ΔPes: -8.37 ± 0.84 vs. -5.90 ± 1.30 cmH(2)0, P ≤ 0.04; tidal volume: 1,193.36 ± 101.85 vs. 1,015.14 ± 119.83 ml, P ≤ 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 ± 0.13 fraction of baseline, P ≤ 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events.     

Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats

Respiratory long-term facilitation (LTF), a serotonin-dependent, persistent augmentation of respiratory activity after episodic hypoxia, is enhanced by pretreatment of chronic intermittent hypoxia (CIH; 5 min 11-12% O2-5 min air, 12 h/night for 7 nights). The present study examined the effects of methysergide (serotonin 5-HT1,2,5,6,7 receptor antagonist), ketanserin (5-HT2 antagonist), or clozapine (5-HT2,6,7 antagonist) on both ventilatory LTF and the CIH effect on ventilatory LTF in conscious male adult rats to determine which specific receptor subtype(s) is involved. In untreated rats (i.e., animals not exposed to CIH), LTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O2) separated by 5-min normoxic intervals, was measured twice by plethysmography. Thus the measurement was conducted 1-2 days before (as control) and approximately 1 h after systemic injection of methysergide (1 mg/kg ip), ketanserin (1 mg/kg), or clozapine (1.5 mg/kg). Resting ventilation, metabolic rate, and hypoxic ventilatory response (HVR) were unchanged, but LTF ( approximately 18% above baseline) was eliminated by each drug. In CIH-treated rats, LTF was also measured twice, before and approximately 8 h after CIH. Vehicle, methysergide, ketanserin, or clozapine was injected approximately 1 h before the second measurement. Neither resting ventilation nor metabolic rate was changed after CIH and/or any drug. HVR was unchanged after methysergide and ketanserin but reduced in four of seven clozapine rats. The CIH-enhanced LTF ( approximately 28%) was abolished by methysergide and clozapine but only attenuated by ketanserin (to approximately 10%). Collectively, these data suggest that ventilatory LTF requires 5-HT2 receptors and that the CIH effect on LTF requires non-5-HT2 serotonin receptors, probably 5-HT6 and/or 5-HT7 subtype(s).     

Exposure to intermittent hypoxia impairs learning and memory ability in rats

To study the effects of chronic intermittent hypoxia (CIH) on learning and memory ability in Sprague–Dawley rats, we established a rat model of CIH. A total of 24 male Sprague–Dawley rats were included and were assigned to three experimental groups (n = 8/group): the unhandled control (UC) group (normal feeding for 4 weeks), the CIH group (CIH for 4 weeks), and the removal of hypoxia (RH) group (normal feeding for 4 weeks after CIH for 4 weeks). All the results were analyzed using one-way ANOVA and comparison between groups was performed using S–N–K method. Performance on the Morris water maze test (a learning and memory test) was significantly worse for CIH rats than for UC rats and RH rats (P < 0.05), but was significantly better for RH rats than for UC rats (P < 0.05). Synaptophysin expression in the CA3 region of the hippocampus was reduced in the CIH group and the RH group compared with the UC group (P < 0.05), but was significantly greater in the RH group than in the CIH group (P < 0.05). Synaptophysin is a calcium-binding protein located in the membranes of presynaptic vesicles. Changes of synaptophysin expression may indirectly reflect the structural changes in the hippocampal CA3 region. In rats, CIH can cause declines in learning ability and memory and reduce the expression of synaptophysin in the CA3 region of the hippocampus; these effects could be partially rescued by the removal of hypoxic factors. The observed decline in learning and memory ability in rats may relate to a decrease in synapse quantity and structural changes in the CA3 region of the hippocampus.

     

Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both.

Adult male rats were anesthetized and catheters were implanted in the caudal artery. Soon after recovery from short-lasting anesthesia, a total of 20 groups of six each were individually exposed to five different oxygen levels varying from 21.0 to 9.0% combined with four CO2 levels ranging from 0 to 12.9% at a mean barometric pressure of 744 Torr. Arterial blood samples were collected and analyzed for pH, Po2, and Pco2 before and near the end of 20-min exposures. During an air-breathing control period, pH averaged 7.466 plus or minus 0.020 SD, Paco2 41.2 plus or minus 1.9 Torr and Pao2 91.8 plus or minus 3.5 Torr. During hypoxia, Pao2 levels were similar to that of acutely hypoxic humans. Rats apparently differ from man in that blood buffering is greater, resulting in a higher pH during air breathing and a smaller [H-+] increase with increasing Paco2. Differences between arterial and inspired CO2 were about 10 Torr at 60 and 90 Torr Plco2 and were not influenced by Plo2.     

NO-dependent effects during adaptation of rats to intermittent hypoxia

In experiments on Wistar rats processes nitric oxide production on concentration of anions (NO2-, NO3-), carbamide and polyamines contents were investigated in processes of rats adaptation to acute hypoxia (7% O2 in N2, 30 min) and intermittent hypoxia training (10% O2 in N2, 15 min, 5 cycles daily) during 14 days. NO production by oxygen-dependent and oxygen-independent metabolites paths has been investigated. It is concluded that the disturbances in nitric oxide system induced by acute hypoxia by L-arginine injections may result in acute hypoxia.     

Plasticity in respiratory motor control: intermittent hypoxia and hypercapnia activate opposing serotonergic and noradrenergic modulatory systems.

Experimental results consistently show that the respiratory control system is plastic, such that environmental factors and experience can modify its performance. Such plasticity may represent basic neurobiological principles of learning and memory, whereby intermittent sensory stimulation produces long-term alterations (i.e. facilitation or depression) in synaptic transmission depending on the timing and intensity of the stimulation. In this review, we propose that intermittent chemosensory stimulation produces long-term changes in respiratory motor output via specific neuromodulatory systems. This concept is based on recent data suggesting that intermittent hypoxia produces a net long-term facilitation of respiratory output via the serotonergic system, whereas intermittent hypercapnia produces a net long-term depression by a mechanism associated with the noradrenergic system. There is suggestive evidence that, although both respiratory stimuli activate both modulatory systems, the balance is different. Thus, these opposing modulatory influences on respiratory motor control may provide a 'push-pull' system, preventing unchecked and inappropriate fluctuations in ventilatory drive.     

Naloxone accelerates the rate of ventilatory acclimatization to hypoxia in awake rats

During ventilatory acclimatization to hypoxia in rats, PaCO2 progressively falls from about 40 torr in normoxia (PIO2 approximately equal to 150 torr) to a new steady-state at about 23 torr in chronic hypoxia (24 or more hours at PIO2 approximately equal to 90 torr). In acute (20 or 60 minutes) hypoxia naloxone treatment caused a hyperventilation greater than that caused by acute hypoxia alone. Following 20 minutes hypoxia, naloxone treated rats had a PaCO2 = 28.6 +/- 0.7 torr (mean +/- 95% confidence limits) which was significantly lower (P less than .001) than the saline treated PaCO2 = 31.0 +/- 0.6 torr. In contrast, in normoxia and at 24 hour hypoxia and at 20 minute return to normoxia following 24 hours hypoxia, naloxone treatment had no effect on PaCO2. We conclude that in the rat about one third of the ventilatory acclimatization to hypoxia is due to a progressively decreasing endogenous opioid-like inhibition of ventilation.     

Left ventricular dysfunction and associated cellular injury in rats exposed to chronic intermittent hypoxia.

Obstructive sleep apnea (OSA) increases cardiovascular morbidity and mortality. We have reported that chronic intermittent hypoxia (CIH), a direct consequence during OSA, leads to left ventricular (LV) remodeling and dysfunction in rats. The present study is to determine LV myocardial cellular injury that is possibly associated with LV global dysfunction. Fifty-six rats were exposed either to CIH (nadir O(2) 4-5%) or sham (handled normoxic controls, HC), 8 h/day for 6 wk. At the end of the exposure, we studied LV global function by cardiac catheterization, and LV myocardial cellular injury by in vitro analyses. Compared with HC, CIH animals demonstrated elevations in mean arterial pressure and LV end-diastolic pressure, but reductions in cardiac output (CIH 141.3 +/- 33.1 vs. HC 184.4 +/- 21.2 ml x min(-1) x kg(-1), P < 0.01), maximal rate of LV pressure rise in systole (+dP/dt), and maximal rate of LV pressure fall in diastole (-dP/dt). CIH led to significant cell injury in the left myocardium, including elevated LV myocyte size, measured by cell surface area (CIH 3,564 +/- 354 vs. HC 2,628 +/- 242 microm(2), P < 0.05) and cell length (CIH 148 +/- 23 vs. HC 115 +/- 16 microm, P < 0.05), elevated terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-stained positive cell number (CIH 98 +/- 45 vs. HC 15 +/- 13, P < 0.01), elevated caspase-3 activity (906 +/- 249 vs. 2,275 +/- 1,169 pmol x min(-1) x mg(-1), P < 0.05), and elevated expression of several remodeling gene markers, including c-fos, atrial natriuretic peptide, beta-myosin heavy chain, and myosin light chain-2. However, there was no difference between groups in sarcomere contractility of isolated LV myocytes, or in LV collagen deposition on trichrome-stained slices. In conclusion, CIH-mediated LV global dysfunction is associated with myocyte hypertrophy and apoptosis at the cellular level.     

Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups.

Carotid bodies are functionally immature at birth and exhibit poor sensitivity to hypoxia. Previous studies have shown that continuous hypoxia at birth impairs hypoxic sensing at the carotid body. Intermittent hypoxia (IH) is more frequently experienced in neonatal life. Previous studies on adult animals have shown that IH facilitates hypoxic sensing at the carotid bodies. On the basis of these studies, in the present study we tested the hypothesis that neonatal IH facilitates hypoxic sensing of the carotid body and augments ventilatory response to hypoxia. Experiments were performed on 2-day-old rat pups that were exposed to 16 h of IH soon after the birth. The IH paradigm consisted of 15 s of 5% O2 (nadir) followed by 5 min of 21% O2 (9 episodes/h). In one group of experiments (IH and control, n = 6 pups each), sensory activity was recorded from ex vivo carotid bodies, and in the other (IH and control, n = 7 pups each) ventilation was monitored in unanesthetized pups by plethysmography. In control pups, sensory response of the carotid body was weak and was slow in onset (approximately 100 s). In contrast, carotid body sensory response to hypoxia was greater and the time course of the response was faster (approximately 30 s) in IH compared with control pups. The magnitude of the hypoxic ventilatory response was greater in IH compared with control pups, whereas changes in O2 consumption and CO2 production during hypoxia were comparable between both groups. The magnitude of ventilatory stimulation by hyperoxic hypercapnia (7% CO2-balance O2), however, was the same between both groups of pups. These results demonstrate that neonatal IH facilitates carotid body sensory response to hypoxia and augments hypoxic ventilatory chemoreflex.