Increased hypoxic ventilatory response during 8 weeks at 3800 m altitude

Acclimatization to chronic hypoxia (CH) increases ventilation (V(I)) and the isocapnic hypoxic ventilatory response (HVR) over 2-14 days but hypoxic desensitization blunts the HVR after years of CH. We tested for hypoxic desensitization during the first 2 months of CH by studying five normal subjects at sea level (SL) and for 8 weeks at 3800 m (CH, PI(O(2)) approximately 90 Torr). We measured the isocapnic HVR (Delta V(I)/Delta Sa(O(2)) and tested for hypoxic ventilatory decline (HVD) by stepping Sa(O(2)) to 80% after 14 min at 90%. The HVR increased significantly after 2 days and remained significantly elevated for 8 weeks of CH. HVD was similar at SL and during 8 weeks of CH. Hence, hypoxic desensitization of the HVR does not occur after only 8 weeks of hypoxia and the increased HVR during this time does not involve changes in HVD.     

Pontine GABAergic pathways: role and plasticity in the hypoxic ventilatory response

The hypoxic ventilatory response (HVR) was compared before and after uni- and bi-lateral injections of bicuculline, a GABA(A) receptor antagonist, into the ventrolateral (vl) pons and before and after conditioning animals to chronic sustained hypoxia (CSH). The HVR was assessed by recording phrenic nerve activity (PNA) during and after brief exposures to hypoxia (8% O(2) and 92% N(2) for 45s). Inspiratory (T(I)) and expiratory (T(E)) durations were averaged before hypoxia, at the peak breathing frequency during hypoxia, before the end of hypoxia, immediately after hypoxia, and 60s after hypoxia. Blocking GABA(A) receptors in the vl pons prolonged T(E) during, but not after hypoxia. After CSH induced by 14 days in a hypobaric chamber (0.5atm), the HVR was attenuated compared to that in the naive animals. This plasticity of HVR was associated with selective induction of alpha6 and delta GABA(A) receptor subunit mRNAs specifically in the pons compared to the medulla. These physiological and molecular results illustrate the importance of pontine GABAergic pathways in shaping the response to hypoxia.     

Physiological responses to prolonged aquatic hypoxia in the Queensland lungfish Neoceratodus forsteri

The effects of moderate and severe hypoxia on air breathing frequency and respiratory properties of the blood of the Queensland (Australian) lungfish Neoceratodus forsteri were measured in fish exposed to these conditions for 14-22 days at 20 degrees C. Haemoglobin oxygen affinity increased after exposure to moderate hypoxia (PW(O(2)) = 60 mmHg), but did not increase further after exposure to severe hypoxia (PW(O(2)) = 40 mmHg). The P(50) of whole blood (20 degrees C, P(CO(2)) = 16.0 mmHg) fell from 22.0 +/- 1.5 mmHg in normoxic conditions to 19.0 +/- 1.0 mmHg in hypoxic conditions. Under both moderate and severe hypoxia, haematocrit, haemoglobin, blood lactate, and erythrocyte phosphate concentrations did not differ from normoxic values. The observed increase in haemoglobin oxygen affinity in response to aquatic hypoxia is typical of compensatory responses seen in obligate water breathers, but smaller. This suggests that the capacity of lungfish to respond to hypoxia by breathing air removes the necessity for further left-shifting of the oxygen equilibrium curve.     

Chronic hypoxia modulates NMDA-mediated regulation of the hypoxic ventilatory response in an amphibian, Bufo marinus

This study examined whether a hypoxia-tolerant amphibian, the Cane toad, undergoes mammalian-like ventilatory acclimatisation to hypoxia (VAH) and whether chronic hypoxia (CH) alters NMDA-mediated regulation of the acute hypoxic ventilatory response (HVR). Toads were exposed to 10 days of CH (10% O2) followed by acute hypoxic breathing trials or an intra-arterial injection of NaCN. Trials were conducted before and after i.p. treatment with an NMDA-receptor channel blocker (MK801). CH blunted the acute HVR but did not alter resting breathing. MK801 did not alter resting ventilation. In control animals, MK801 augmented breathing frequency (fR) during acute hypoxia by increasing the number of breaths per episode. This effect was attenuated following CH although MK801 did enhance the number of episodes per minute during acute hypoxia. MK801 enhanced the fR response to NaCN in both groups. The results indicate that CH did not produce mammalian-like VAH (i.e. increased resting ventilation and an augmented acute HVR) but did alter MK801-sensitive regulation of breathing pattern and the acute HVR.     

Effects of enhanced human chemosensitivity on ventilatory responses to exercise

It is not clear what the effects of different types of intermittent hypoxia have on human exercise ventilation. The purpose of this study was to determine whether short-duration intermittent hypoxia, and the subsequent augmentation of the hypoxic ventilatory response (HVR), would lead to an increase in ventilatory responses during exercise at sea level. It was hypothesized that subjects exposed to short-duration intermittent hypoxia would have a greater increase in the ventilatory response to exercise compared to those exposed to long-duration intermittent hypoxia. Subjects (n = 17, male) were randomly assigned to short-duration intermittent hypoxia (SDIH: 5 min of 12% O2 separated by 5 min of normoxia for 1 h) or long-duration intermittent hypoxia (LDIH: 30 min of 12% O2). Both groups had 10 exposures over a 12 day period. The HVR was measured on days 1 and 12. Maximal oxygen consumption (VO2max) was determined using a ramped cycle exercise test. Maximal exercise data were not different (P > 0.05) between SDIH and LDIH groups or following intermittent hypoxia. Minute ventilation, tidal volume and respiratory frequency were compared at 20, 40, 60, 80 and 100% of VO2max . There was no difference in the ventilatory responses at any intensity of exercise following the intermittent hypoxia period. The HVR was significantly increased following the intermittent hypoxia intervention (P < 0.05) but was not different between SDIH and LDIH (P > 0.05). The relationships between HVR and VO2max were non-significant on day 1 (r = 0.30) and day 12 (r = 0.47; P > 0.05). Our findings point to a lack of functional significance of increasing HVR via intermittent hypoxia on ventilatory responses to exercise at sea level.     

Cerebral blood flow sensitivity to CO2 measured with steady-state and Read's rebreathing methods

The ventilatory response to carbon dioxide (CO2) measured by the steady-state method is lower than that measured by Read's rebreathing method. A change in end-tidal P CO2 (PET CO2) results in a lower increment change in brain tissue P CO2 (Pt CO2) in the steady-state than with rebreathing: since Pt(CO2) determines the ventilatory response to CO2, the response is lower in the steady-state. If cerebral blood flow (CBF) responds to Pt CO2, the CBF-CO2 response should be lower in the steady-state than with rebreathing. Six subjects undertook two protocols, (a) steady-state: PET CO2 was held at 1.5 mmHg above normal (isocapnia) for 10 min, then raised to three levels of hypercapnia, (8 min each; 6.5, 11.5 and 16.5 mmHg above normal, separated by 4 min isocapnia). End-tidal P O2 was held at 300 mmHg; (b) rebreathing: subjects rebreathed via a 6 L bag filled with 6.5% CO2 in O2. Transcranial Doppler-derived CBF yielded a higher CBF-CO2 sensitivity in the steady-state than with rebreathing, suggesting that CBF does not respond to Pt CO2.     

Repeated measurement of hypoxic ventilatory response as an intermittent hypoxic stimulus

Measurement of hypoxic ventilatory response (HVR) involves an exposure to hypoxia which, if repeated over several days might act as an intermittent hypoxic stimulus. The purpose of this study was to measure HVR repeatedly over 5 days to determine whether it was affected by repeated measurement. Nine healthy male subjects completed an isocapnic HVR test, on one occasion, followed 5 days later by one measurement each day for 5 days. Each test lasted approximately 5-8 min with inspired oxygen concentration declining to as a low as 5-6%. No systematic trend was observed in HVR over the 5-day period (p>0.05). There were no significant differences in HVR between any of the test days. Regression failed to show any trend in HVR over the five sequential days. The calculated mean coefficient of variation for HVR for each subject was 27%. There is no evidence that the short exposure to hypoxia as part of HVR measurement is a co-intervention when measured repeatedly over 5 days in physiological studies.     

Low-dose acetazolamide reduces the hypoxic ventilatory response in the anesthetized cat

Low intravenous dose acetazolamide causes a decrease in steady-state CO(2) sensitivity of both the peripheral and central chemoreflex loops. The effect, however, on the steady-state hypoxic response is unknown. In the present study, we measured the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the isocapnic steady-state hypoxic response in anesthetized cats. Before and after acetazolamide administration, the eucapnic steady-state hypoxic response in these animals was measured by varying inspiratory P(O2) levels to achieve steady-state Pa(O2) levels between hyperoxia Pa(O2) approximately 55 kPa, approximately 412 mmHg) and hypoxia (Pa(O2) approximately 7 kPa, approximately 53 mmHg). The hypoxic ventilatory response was described by the exponential function V(I) = G exp (-DP(o2) + A with an overall hypoxic sensitivity G, a shape parameter D and ventilation during hyperoxia A. Acetazolamide significantly reduced G from 3.057 +/- 1.616 to 1.573 +/- 0.8361 min(-1) (mean +/- S D). Parameter A increased from 0.903 +/- 0.257 to 1.193 +/- 0.321 min(-1), while D remained unchanged. The decrease in overall hypoxic sensitivity by acetazolamide is probably mediated by an inhibitory effect on the carotid bodies and may have clinical significance in the treatment of sleep apneas, particularly those cases that are associated with an increased ventilatory sensitivity to oxygen and/or carbon dioxide.     

The effect of hypoxia on pulmonary O2 uptake, leg blood flow and muscle deoxygenation during single-leg knee-extension exercise

The effect of hypoxic breathing on pulmonary O(2) uptake (VO(2p)), leg blood flow (LBF) and O(2) delivery and deoxygenation of the vastus lateralis muscle was examined during constant-load single-leg knee-extension exercise. Seven subjects (24 +/- 4 years; mean +/-s.d.) performed two transitions from unloaded to moderate-intensity exercise (21 W) under normoxic and hypoxic (P(ET)O(2)= 60 mmHg) conditions. Breath-by-breath VO(2p) and beat-by-beat femoral artery mean blood velocity (MBV) were measured by mass spectrometer and volume turbine and Doppler ultrasound (VingMed, CFM 750), respectively. Deoxy-(HHb), oxy-, and total haemoglobin/myoglobin were measured continuously by near-infrared spectroscopy (NIRS; Hamamatsu NIRO-300). VO(2p) data were filtered and averaged to 5 s bins at 20, 40, 60, 120, 180 and 300 s. MBV data were filtered and averaged to 2 s bins (1 contraction cycle). LBF was calculated for each contraction cycle and averaged to 5 s bins at 20, 40, 60, 120, 180 and 300 s. VO(2p) was significantly lower in hypoxia throughout the period of 20, 40, 60 and 120 s of the exercise on-transient. LBF (l min(-1)) was approximately 35% higher (P > 0.05) in hypoxia during the on-transient and steady-state of KE exercise, resulting in a similar leg O(2) delivery in hypoxia and normoxia. Local muscle deoxygenation (HHb) was similar in hypoxia and normoxia. These results suggest that factors other than O(2) delivery, possibly the diffusion of O(2,) were responsible for the lower O(2) uptake during the exercise on-transient in hypoxia.     

Serotoninergic receptors in the anteroventral preoptic region modulate the hypoxic ventilatory response

Hypothalamus is a site of integration of the hypoxic and thermal stimuli on breathing and there is evidence that serotonin (5-HT) receptors in the anteroventral preoptic region (AVPO) mediate hypoxic hypothermia. Once 5-HT is involved in the hypoxic ventilatory response (HVR), we investigated the participation of the 5-HT receptors (5-HT1, 5-HT2 and 5-HT7) in the AVPO in the HVR. To this end, pulmonary ventilation (V(E)) of rats was measured before and after intra-AVPO microinjection of methysergide (a 5-HT1 and 5-HT2 receptor antagonist), WAY-100635 (a 5-HT1A receptor antagonist) and SB-269970 (a 5-HT7 receptor antagonist), followed by 60 min of hypoxia exposure (7% O2). Intra-AVPO microinjection of vehicles or 5-HT antagonists did not change V(E) during normoxic conditions. Exposure of rats to 7% O2 evoked typical hypoxia-induced hyperpnea after vehicle microinjection, which was not affected by methysergide. WAY-100635 and SB-269970 treatment caused an increased HVR, due to a higher tidal volume. Therefore, the current data provide the evidence that 5-HT acting on 5-HT1A and 5-HT7 receptors in the AVPO exert an inhibitory modulation on the HVR.     

Maturation of the initial ventilatory response to hypoxia in sleeping infants

In infants most previous studies of the hypoxic ventilatory response (HVR) have been conducted only during quiet sleep (QS) and arousal responses have not been considered. Our aim was to quantify the maturation of the HVR in term infants during both active sleep (AS) and QS over the first 6 months of life. Daytime polysomnography was performed on 15 healthy term infants at 2-5 weeks, 2-3 and 5-6 months after birth and infants were challenged with hypoxia (15% O2, balance N2). Tests in AS always resulted in arousal; in QS tests infants either aroused or did not arouse. A biphasic HVR was observed in non arousing tests at all three ages studied. The fall in SpO2 was more rapid in arousal tests at all three ages. At 2-5 weeks, in non-arousing QS tests, there was a greater fall in respiratory frequency (f) despite a smaller fall in SpO2 compared with 2-3 and 5-6 months. When infants aroused there was no difference in the HVR between sleep states or with postnatal age. However, when infants failed to arouse from QS, arterial desaturation was less in the younger infants despite a poorer HVR. We suggest that arousal in response to hypoxia, particularly in AS, is a vital survival mechanism throughout the first 6 months of life.     

Modification of hypoxic pulmonary vasoconstriction by aerosolized cromolyn sodium

We have previously demonstrated the role of mast cell degranulation in the mediation of hypoxic pulmonary vasoconstriction, and its prevention by intravenous cromolyn sodium. In the present investigation, we studied the modification of the hypoxic pulmonary vascular response by aerosolized cromolyn sodium. In seven conscious sheep on two separate days, pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output were measured for the calculation of pulmonary vascular resistance (Rpv) along with arterial oxygen tension (Pao2) during room air breathing and breathing a hypoxic gas mixture (13% O2-87% N2), without and with cromolyn sodium administration. Cromolyn sodium (20 mg X kg-1) was administered as an aerosol before and during 13% O2 breathing. The sheep had comparable degrees of hypoxia during low oxygen breathing on both days (mean PaO2: 43 and 46 mmHg). Breathing hypoxic gas mixture caused pulmonary vasoconstriction, with increases in mean Rpv of 89% (p less than 0.05). Aerosolized cromolyn sodium blunted the hypoxic pulmonary vascular response; mean Rpv increased by 27% (p less than 0.05), which was significantly different from the increase during hypoxia without cromolyn sodium treatment (p less than 0.05). We conclude that aerosolized cromolyn sodium (a mast cell membrane stabilizing agent) modifies hypoxic pulmonary vasoconstriction; however, unlike the intravenous form, aerosolized cromolyn sodium (at the dosage used) offers a partial protection.     

Ventilatory responses to isocapnic and poikilocapnic hypoxia in humans

We examined the hypoxic ventilatory response (HVR) including breathing frequency (f(R)) and tidal volume (V(T)) responses during 20 min of step isocapnic (IH) and poikilocapnic (PH) hypoxia (45 Torr). We hypothesized an index related to [Formula: see text] (pHPR) may be more robust during PH. Peak HVR was suppressed during PH (P<0.001), and mediated by V(T) during PH and both V(T) and f(R) during IH. The relative magnitude of HVD remained similar between conditions indicating a suppressive role of hypocapnia in development of the HVR unrelated to the degree of subsequent HVD, implying a primarily O(2) dependant mechanism. Post-hypoxic frequency decline was observed following both IH (3.4+/-3.7 bpm, P<0.05) and PH (3.6+/-3.1 bpm, P<0.01), despite no f(R) response during exposure to PH. Use of pHPR improved the signal to noise ratio during PH, though failed to detect the peak ventilatory response, and therefore may not be appropriate when describing peak responses.     

Lack of gender difference in ventilatory chemoresponsiveness and post-hypoxic ventilatory decline

Altered chemoresponsiveness has been postulated to explain the gender difference in the incidence of sleep disordered breathing (SDB). The purpose of this investigation was to ascertain a gender difference in the effect of hypocapnic hypoxia on ventilation. Hypocapnic hypoxia was induced in stable NREM sleep for 3 min periods. In the first analysis, hypoxic ventilatory response in a steady state (SHVR) was defined as the amount of change in minute ventilation (VI) between mean room air (RA) and hypoxia divided by the change in Sa O2 between RA and hypoxia (DeltaVI/DeltaSa O2). The mean group SHVR values were 0.23+/-0.15 and 0.20+/-0.10 L/min per %SaO2, for men and women, respectively (P = ns). In the second analysis, we analyzed the decline in ventilatory parameters after the cessation of hypoxia. There was no difference in VI between the genders (men, 5.6+/-1.7 L/min vs. women, 4.9+/-1.9 L/min, P = ns). We conclude that the gender difference in SDB is not explained by a difference in the ventilatory response to hypocapnic hypoxia.     

Enhanced chemosensitivity after intermittent hypoxic exposure does not affect exercise ventilation at sea level

The purpose of the present study was to test the hypothesis that the ventilatory response to exercise at sea level may increase after intermittent hypoxic exposure for 1 week, accompanied by an increase in hypoxic or hypercapnic ventilatory chemosensitivity. One group of eight subjects (hypoxic group) were decompressed in a chamber to 432 torr (where 1 torr=1.0 mmHg, simulating an altitude of 4,500 m) over a period of 30 min and maintained at that pressure for 1 h daily for 7 days. Oxygen uptake and pulmonary ventilation (V_E) were determined at 40%, 70%, and 100% of maximal oxygen uptake at sea level before (Pre) and after (Post) 1 week of daily exposures to hypoxia. The hypoxic ventilatory response (HVR) was determined using the isocapnic progressive hypoxic method as an index of ventilatory chemosensitivity to hypoxia, and the hypercapnic ventilatory response (HCVRSB) was measured by means of the single-breath carbon dioxide method as an index of peripheral ventilatory chemosensitivity to hypercapnia. The same parameters were measured in another group of six subjects (control group). In the hypoxic group, resting HVR increased significantly (P<0.05) after intermittent hypoxia and HCVRSB increased at Post, but the change was not statistically significant (P=0.07). In contrast, no changes in HVR and HCVRSB were found in the control group. There were no changes in either V_E or the ventilatory equivalent for oxygen during maximal and submaximal exercise at sea level throughout the experimental period in either group. These results suggest that the changes in resting hypoxic and peripheral hypercapnic chemosensitivities following short-term intermittent hypoxia have little effect on exercise ventilation at sea level. Electronic Publication     

Cardioventilatory effects of acclimatization to aquatic hypoxia in channel catfish

The mechanisms responsible for altering cardioventilatory control in vertebrates in response to chronic hypoxia are not well understood but appear to be mediated through the oxygen-sensitive chemoreceptor pathway. Little is known about the effects of chronic hypoxia on cardioventilatory control in vertebrates other than mammals. The purpose of this study was to determine how cardioventilatory control and the pattern of response is altered in channel catfish (Ictalurus punctatus) by 1 week of moderate hypoxia. Fish were acclimatized for 7 days in either normoxia (P(O(2)) approximately 150 Torr) or hypoxia (P(O(2)) approximately 75 Torr). After acclimatization, cardioventilatory, blood-gas and acid/base variables were measured during normoxia (P(O(2)) 148+/-1 Torr) then at two levels of acute (5 min) hypoxia, (P(O(2)) 72.6+/-1 and 50.4+/-0.4 Torr). Ventilation was significantly greater in hypoxic acclimatized fish as was the ventilatory sensitivity to hypoxia (Delta ventilation/Delta P(O(2))). The increase in ventilation and hypoxic sensitivity was due to increases in opercular pressure amplitude, gill ventilation frequency did not change. Heart rate was greater in hypoxic acclimatized fish but decreased in both acclimatization groups in response to acute hypoxia. Heart rate sensitivity to hypoxia (Delta heart rate/Delta P(O(2))) was not affected by hypoxic acclimatization. The ventilatory effects of hypoxic acclimatization can be explained by increased sensitivity to oxygen but the effects on heart rate cannot.     

Suggested predictive indices for high altitude pulmonary oedema

A study was conducted to evaluate the responses of chemoreceptors and pulmonary vascular bed to hypoxia, on two groups of soldiers exposed to similar altitudes, one group which did not suffer from high altitude (HA) maladies (Gp A) and the other when exposed to similar altitudes suffered from HA maladies (Gp B high altitude pulmonary edema--susceptible group (HAPE-S). Aim of this study was to find out whether these two tests could be used as a screening test for soldiers and sojourners proceeding to HA. Chemoreceptor responses were evaluated by hypoxic ventilatory response (HVR) test and the pulmonary vascular responses were studied by recording pulmonary artery pressure (PAP) changes under simulated hypoxia by breathing hypoxic gas mixtures (HGM) in both the groups. It was observed that HAPE-S subjects showed a reduced HVR response and an increase in PAP (systolic, diastolic, and mean). While Gp A subjects showed an increase in ventilation of 11.39 +/- 3.36 L, the same in Gp B subjects was 3.51 +/- 2.65 L. Thus, the comparison of increase in ventilation following HVR test between the two groups was highly significant. Under hypoxic gas mixture (HGM) breathing, systolic pressure of 28.2 +/- 6.9 and 52.6 +/- 11.0 mm Hg; diastolic pressure of 11.4 +/- 3.8 and 23.6 +/- 5.8 mm Hg and mean pressure of 17.6 +/- 4.3 and 35.0 +/- 7.4 mm Hg were recorded in pulmonary arteries in Gp A and Gp B subjects, respectively. Gp B subjects showed a highly significant increase in all the three pulmonary pressures under HGM breathing.     

Short-term effects of normobaric hypoxia on the human spleen

Spleen contraction resulting in an increase in circulating erythrocytes has been shown to occur during apnea. This effect, however, has not previously been studied during normobaric hypoxia whilst breathing. After 20 min of horizontal rest and normoxic breathing, five subjects underwent 20-min of normobaric hypoxic breathing (12.8% oxygen) followed by 10 min of normoxic breathing. Ultrasound measurements of spleen volume and samples for venous hemoglobin concentration (Hb) and hematocrit (Hct) were taken simultaneously at short intervals from 20 min before until 10 min after the hypoxic period. Heart rate, arterial oxygen saturation (SaO(2)) and respiration rate were recorded continuously. During hypoxia, a reduction in SaO(2) by 34% (P < 0.01) was accompanied by an 18% reduction in spleen volume and a 2.1% increase in both Hb and Hct (P < 0.05). Heart rate increased 28% above baseline (P < 0.05). Within 3 min after hypoxia SaO(2) had returned to pre-hypoxic levels, and spleen volume, Hb and Hct had all returned to pre-hypoxic levels within 10 min. Respiratory rate remained stable throughout the protocol. This study of short-term exposure to eupneic normobaric hypoxia suggests that hypoxia plays a key role in triggering spleen contraction and subsequent release of stored erythrocytes in humans. This response could be beneficial during early altitude acclimatization.     

Respiratory and neuroendocrine responses of piglets to hypoxia during postnatal development

Breathing response to 12% and 6% O2 in N2 (at isocapnia) was measured in anaesthetized piglets, 1-5 and 19-25 days old, before and after 3 mg kg-1 i.v. naltrexone. The degree of interaction between the anaesthetic and naltrexone was assessed. At the end of each hypoxic trial, arterial blood was sampled for measurements of pH and gas tensions, (Met)enkephalin-Arg6-Phe7, adenosine, noradrenaline and adrenalin. Whereas respiration in older animals was stimulated by hypoxia, young piglets had a biphasic response with a pronounced ventilatory decrease in response to severe hypoxia (6% O2/N2). In young animals there was a greater ventilatory response with naltrexone than without the drug, and the biphasic hypoxic response was ameliorated or reversed by naltrexone. Levels of adrenalin increased and those of encephalin, adenosine and noradrenaline tended to increase during hypoxia in the younger age group. Levels of adenosine showed significant increase when data from both age groups and levels of hypoxia were pooled. Combined with previously reported physiological evidence regarding adenosine in hypoxic depression, we conclude that the present results are compatible with a role of opioid peptides and adenosine in the early postnatal response to hypoxia.     

Hypoxic ventilatory response of adult rats and mice after developmental hyperoxia

Chronic postnatal hyperoxia attenuates the hypoxic ventilatory response (HVR) of rats. To determine whether the ability to detect deficits in the HVR depends on the degree of hypoxia, we assessed the HVR at several levels of hypoxia in adult rats reared in 60% O(2) for the first two postnatal weeks. Hyperoxia-treated rats exhibited smaller increases in ventilation than control rats at 12% O(2) (30±8 vs. 53±4% baseline, mean±SEM; P=0.02) but not at 10% O(2) (83±11 vs. 96±14% baseline; P=0.47). Interestingly, 10% O(2) was used as the test gas in the only study to assess HVR in mice exposed to developmental hyperoxia, and that study reported normal HVR (Dauger et al., Chest 123 (2003), 530-538). Therefore, we assessed the HVR at 12.5% O(2) in adult mice reared in 60% O(2) for the first two postnatal weeks. Hyperoxia-treated mice exhibited smaller increases in ventilation (28±7 vs. 58±8% baseline; P<0.01) and smaller carotid bodies than control mice. We conclude that hyperoxia impairs the HVR in both rats and mice, but this effect is most evident at moderate levels of hypoxia.