Oxygen transport to exercising leg in chronic hypoxia

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.     

Separate effects of low carbon dioxide and low oxygen content on rat brain monoamine metabolism during hypoxemia

Awake, adult male rats (some with chronically indwelling femoral artery catheters) were exposed for up to 7 days to one of three environments: a) normoxia (PIO2 = 155 Torr), b) hypoxic hypocapnia (PIO2 = 90 Torr), and c) hypoxic normocapnia (PIO2 = 73 Torr, PICO2 = 32 Torr), and arterial blood gas and acid-base status were documented. After 1 hour to 7 days, rats were sacrificed, and the time courses of the brain levels and turnovers of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine or 5HT) were determined in each condition. The transient decrease in monoamine levels seen on exposure to acute hypoxia was absent if normocapnia was maintained; 7 days hypoxia with or without hypocapnia resulted in increased monoamine levels. Normocapnia also prevented an immediate, sustained decrease in 5HT turnover and a delayed decrease in DA turnover which were observed in hypoxic hypocapnia. A delayed increase in 5HT turnover appeared to be due to hypoxia independent of PaCO2. Therefore, the initial, transient loss of mental acuity and some ventilatory adaptations observed during prolonged hypoxia may be a result of the decrease in PaCO2 rather than the decreased oxygen concentration.     

Hypoxia potentiates, oxygen attenuates deflation-induced reflex tracheal constriction

The reflex tracheomotor responses of in situ isolated segments of the extrathoracic trachea of anesthetized, paralyzed, and ventilated dogs were monitored. Reflex tracheal constriction was evoked by passive lung deflation. The purpose of this study was to determine whether the prevailing state of oxygenation altered the magnitude of this reflex. Compared with the magnitude of the response during normoxia [arterial O2 tension (PaO2) = 78 Torr], that during hypoxia (PaO2 = 44 Torr) was nearly threefold larger while that during hyperoxia (PaO2 greater than 250 Torr) was about 50% smaller. The isocapnic changes in oxygenation by themselves usually had no effect on tracheomotor tone. The deflation-induced reflex tracheal constriction was eliminated by complete denervation of the tracheal segment but usually only diminished by partial denervation. Bilateral vagotomies or bilateral carotid body denervation also usually decreased the magnitude of the reflex. It appears that the magnitude of this reflex is dependent on the prevailing state of oxygenation and that a pulmonary stretch receptor-carotid body chemoreceptor interaction accounts for the exaggerated reflex tracheal constriction during hypoxia and the attenuated response during hyperoxia.     

Effects of hypoxia or hyperoxia on the lung of the chick embryo

Newborn mammals in chronic hypoxia or hyperoxia experience, respectively, an increase or decrease in lung weight:body weight ratios, possibly because of the mechanical effect on the lung accompanying the ventilatory response. Because the avian lung does not expand or contract with the breathing cycle, we asked whether or not qualitatively similar changes could be observed in the lung of chick embryos incubated in hypoxic or hyperoxic conditions. Hypoxic embryos (10% O2, days 14-18) were smaller than controls incubated in normoxia, with higher hematocrit values and larger lung weight:body weight ratios (both wet and dry). Both the total pulmonary DNA (reflecting the cellular component) and the DNA concentration were decreased in hypoxia. Hyperoxic embryos (50% O2, days 7-18 or days 14-18) had lower hematocrit values and smaller dry lung weight:body weight ratios than controls, with similar DNA concentrations. In general, the differences from controls were more apparent in those embryos hyperoxic from day 14 to 18 of incubation than from day 7 to 18. We conclude that changes in lung weights qualitatively similar to those occurring in the chronically hypoxic or hyperoxic newborn mammal can also be observed in the hypoxic or hyperoxic chick embryo, suggesting that they are not necessarily caused by changes in mechanical stretch on the lung.     

Ventilation in newborn rats after gestation at simulated high altitude

Pregnant rats were kept at a simulated altitude of 4,500 m (PO2 91 Torr) for the whole of gestation and returned to sea level 1 day after giving birth. During pregnancy, body weight gain and food intake were approximately 30% less than in controls at sea level. Measurements were made on the 1-day-old (HYPO) pups after a few hours at sea level. In normoxia, ventilation (VE) measured by flow plethysmography was more (+17%) and O2 consumption (VO2) measured by a manometric method was less (-19%) than in control (CONT) pups; in HYPO pups VE/VO2 was 44% greater than in CONT pups. In acute hyperoxia, VE/VO2 of HYPO and CONT pups decreased by a similar amount (15-20%), indicating some limitation in O2 availability for both groups of pups in normoxia. However, VE/VO2 of HYPO pups, even in hyperoxia, remained above (+34%) that of CONT pups. HYPO pups weighed slightly less than CONT pups, their lungs were hypoplastic, and their hearts were a larger fraction of body weight. An additional group of female rats was acclimatized (8 days) to high altitude before insemination. During pregnancy, body weight gain and food intake of these females were similar to those of pregnant rats at sea level. Measurements on the 1-day-old pups of this group were similar to those of HYPO pups. We conclude that newborn rats born after hypoxic gestation present metabolic adaptation (low VO2) and acclimatization (high VE/VO2), possibly because of hypoxemia. Maternal acclimatization before insemination substantially alters maternal growth in hypoxia but does not affect neonatal outcome.     

Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep.

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired P(O2). We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78-80%), and hyperoxia (inspired O2 fraction = 50-52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sigh-like breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 +/- 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 +/- 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 +/- 13.8 s; P < 0.01). The apneic threshold end-tidal P(CO2) (Pet(CO2)) was defined as the Pet(CO2)) at the onset of apnea. During hypoxia, the apneic threshold Pet(CO2) was higher (38.9 +/- 1.7 Torr; P < 0.01) compared with normoxia (35.8 +/- 1.1; Torr); during hyperoxia, it was lower (33.0 +/- 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic Pet(CO2) and apneic threshold Pet(CO2) was smaller during hypoxia (3.0 +/- 1.0 Torr P < 001) and greater during hyperoxia (10.6 +/- 0.8 Torr; P < 0.05) compared with normoxia (8.0 +/- 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic Pet(CO2) was increased by hypoxia (3.44 +/- 0.63 l.min(-1).Torr(-1); P < 0.05) and decreased by hyperoxia (0.63 +/- 0.04 l.min(-1).Torr(-1); P < 0.05) compared with normoxia (0.79 +/- 0.05 l.min(-1).Torr(-1)). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.     

Adult carotid chemoafferent responses to hypoxia after 1, 2, and 4 wk of postnatal hyperoxia.

Exposing newborn rats to postnatal hyperoxia (60% O2) for 1-4 wk attenuates the ventilatory and phrenic nerve responses to acute hypoxia in adult rats. The goal of this research was to increase our understanding of the carotid chemoreceptor afferent neural input in this depressed response with different durations of postnatal hyperoxic exposure. Rats were exposed from a few days before birth to 1, 2, or 4 wk of 60% O2 and studied after 3-5 mo in normoxia. The rats were anesthetized with urethane. Whole carotid sinus nerve (CSN) responses to NaCN (40 microg/kg iv), 10 s of asphyxia and acute isocapnic hypoxia (arterial Po2 45 Torr) were determined. Mean CSN responses to stimuli after postnatal hyperoxia were reduced compared with controls. Responses in rats exposed to 1 wk of postnatal hyperoxia were less affected than those exposed to 2 and 4 wk of hyperoxia, which were equivalent to each other. These studies illustrate the importance of normoxia during the first 2 wk of life in development of carotid chemoreceptor afferent function.     

Ventilatory effects and interactions with change in PaO2 in awake goats.

We utilized selective carotid body (CB) perfusion while changing inspired O2 fraction in arterial isocapnia to characterize the non-CB chemoreceptor ventilatory response to changes in arterial PO2 (PaO2) in awake goats and to define the effect of varying levels of CB PO2 on this response. Systemic hyperoxia (PaO2 greater than 400 Torr) significantly increased inspired ventilation (VI) and tidal volume (VT) in goats during CB normoxia, and systemic hypoxia (PaO2 = 29 Torr) significantly increased VI and respiratory frequency in these goats. CB hypoxia (CB PO2 = 34 Torr) in systemic normoxia significantly increased VI, VT, and VT/TI; the ventilatory effects of CB hypoxia were not significantly altered by varying systemic PaO2. We conclude that ventilation is stimulated by systemic hypoxia and hyperoxia in CB normoxia and that this ventilatory response to changes in systemic O2 affects the CB O2 response in an additive manner.     

Effects of altitude acclimatization on pulmonary gas exchange during exercise

Pulmonary gas exchange was studied in eight normal subjects both before and after 2 wk of altitude acclimatization at 3,800 m (12,470 ft, barometric pressure = 484 Torr). Respiratory and multiple inert gas tensions, ventilation, cardiac output (Q), and hemoglobin concentration were measured at rest and during three levels of constant-load cycle exercise during both normoxia [inspired PO2 (PIO2) = 148 Torr] and normobaric hypoxia (PIO2 = 91 Torr). After acclimatization, the measured alveolar-arterial PO2 difference (A-aPO2) for any given work rate decreased (P less than 0.02). The largest reductions were observed during the highest work rates and were 24.8 +/- 1.4 to 19.7 +/- 0.8 Torr (normoxia) and 22.0 +/- 1.1 to 19.4 +/- 0.7 Torr (hypoxia). This could not be explained by changes in ventilation-perfusion inequality or estimated O2 diffusing capacity, which were unaffected by acclimatization. However, Q for any given work rate was significantly decreased (P less than 0.001) after acclimatization. We suggest that the reduction in A-aPO2 after acclimatization is a result of more nearly complete alveolar/end-capillary diffusion equilibration on the basis of a longer pulmonary capillary transit time.     

Food-restricting first generation juvenile female hamsters (Mesocricetus auratus) affects sex ratio and growth of third generation offspring

Female hamsters (Generation 1) were fed ad libitum or were food-restricted to 65-75% of the amount consumed by controls during their first 50 days of life. Subjects were mated at 91 days of age. Their offspring (Generation 2) were fed ad libitum throughout the experiment, and female offspring were also mated at 91 days of age. Generation 3 litters were monitored every fifth day from birth until Day 25 post partum for litter size, sex ratio, and pup weights. Although there were no significant differences in Generation 3 litter sizes at birth, litters descended from food-restricted Generation 1 females (Group R) were significantly smaller on Days 5-25 than litters descended from control Generation 1 females (Group A). Sex ratios remained significantly greater in Group A than in Group R litters from birth to Day 25 but did not vary over time, suggesting similar post-partum mortality rates for both male and female pups. Weights of Generation 3 male and female pups did not vary significantly within treatments at any time. Group A males weighed significantly more than Group R males from birth through Day 25, but weights of Group A and Group R females were always similar. Food restriction early in life may have long-term consequences on sex ratios of subsequent generations in hamsters.     

The incidence of breathing movements of fetal sheep in normoxia and hypoxia after peripheral chemodenervation and brain-stem transection

The incidence of fetal breathing movements and low voltage electrocortical activity was measured in three groups of fetal sheep, at 123-137 days gestation. The first group (transected & denervated) had the brainstem transected at the level of the colliculi and also had peripheral arterial chemodenervation. The second group (denervated) had a sham brain-stem transection and peripheral arterial chemodenervation. The third group (sham-operated) had sham brain-stem transection and sham peripheral chemodenervation. No differences were observed in the incidence of fetal breathing movements or low voltage electrocortical activity between the sham-operated and the denervated groups in normoxia, or in hypoxia when all these fetuses became apnoeic. There were however differences between these 2 groups and the transected & denervated group, in which fetal breathing movements where dissociated from electrocortical activity and which in some fetuses were continuous. During isocapnic hypoxia 3 of 8 transected & denervated fetuses made fetal breathing movements. We discuss the problems of interpreting data from brain-stem transected fetuses, but conclude that the evidence reveals no tonic influence of the peripheral arterial chemoreceptors on fetal breathing movements.     

Litter mixing significantly affects decomposition in the Hulun Buir meadow steppe of Inner Mongolia,China

Aims We explored the decomposition rates of single- and mixed-species litter, the litter-mixing effect and the effect of component litters in a mixture on decomposition.Methods In a litter bag experiment, shoot litters from two dominant grasses (Leymus chinensis and Stipa baicalensis) and one legume (Melissitus ruthenica) were decomposed separately and as a mixture from May 2010 to September 2011 in the Hulun Buir meadow steppe of Inner Mongolia, China. We separated the litter mixture into its individual component litters (i.e. the different single-species litters) and analyzed the changes in litter mass remaining and litter nitrogen (N) remaining during single- and mixed-species litter decomposition.Important findings (i) Litter mixing had significant positive effects on litter decomposition. The litter-mixing effect was strongest for the mixture of S. baicalensis and L. chinensis litters, followed by the mixture of S. baicalensis and M. ruthenica litters. (ii) Single-species component litters decomposed faster in the mixtures than separately (positive effect), but these effects were not significant for legume species M. ruthenica litter. Relative to single-species litter decomposition, the decomposition rates of the two grass (S. baicalensis and L. chinensis) litters significantly increased when they were mixed with each other or with M. ruthenica litter. (iii) For each species litter type, the percentage of litter N remaining during decomposition (N R) differed between the single-species litter and mixed litter treatments. The N R of S. baicalensis litter was higher when it was decomposed in the mixture than in isolation. However, the N R of L. chinensis litter was lowest in its mixture with M. ruthenica among the treatments. Regardless of its decomposition in the mixture or in isolation, the N R of M. ruthenica litter varied little among treatments. There was a significant positive relationship between the N R and percentage of initial litter mass remaining in both the single litter and mixed litter treatments. These results suggest that N transfer may happen among component litters in mixture and further affect the decomposition.     

Supplemental oxygen reduces right ventricular hypertrophy in monocrotaline-injected rats

We evaluated the possible contributory role of hypoxia in the development of monocrotaline-induced pulmonary hypertension. Male Sprague-Dawley rats were injected subcutaneously with monocrotaline (60 mg/kg) or saline in controls and were kept in oxygen-enriched (inspired O2 fraction of 0.35) or compressed air chambers. After 21 days, rats were anesthetized while spontaneously breathing room air, hemodynamic parameters and arterial blood gases were measured, and animals were killed. Right ventricular peak systolic pressures (RVPP), right ventricular-to-left ventricular plus septal weight ratios (RV/LV + S), hematocrits, lung dry weight-to-body weight ratios, and medial thickness of pulmonary arteries were significantly reduced in monocrotaline-injected rats exposed to mild hyperoxia compared with air. The air-exposed monocrotaline-injected rats had significantly more arterial hypoxemia than the other groups, and mild hyperoxia had no effect on any of the measured variables in saline-injected rats. To determine whether the effects of mild hyperoxia occurred early or late after monocrotaline injection, we moved separate groups of rats from air to mild hyperoxia and vice versa 10 days after monocrotaline injection. After 21 days, significant reductions in RVPP and RV/LV + S occurred only in rats exposed to mild hyperoxia during the latter 11 days after injection. Our findings suggest that hypoxia contributes to the development of pulmonary hypertension relatively late after monocrotaline injection in rats but that it does not influence the early injury.     

Effect of 100% O2 on hypoxic eucapnic ventilation

We measured ventilation in nine young adults while they breathed pure O2 after breathing room air and after 5 and 25 min of hypoxia. With isocapnic hypoxia (arterial O2 saturation 80 +/- 2%) mean ventilation increased at 5 min and then declined, so that at 25 min values did not differ from those on room air. After 3 min of O2 breathing, ventilation was greater than that on room air or after 25 min of isocapnic hypoxia, whether the hyperoxia had been preceded by hypoxia or normoxia. During transitions to pure O2 breathing, ventilation was analyzed breath by breath with a moving average technique, searching for nadirs before and after increases in PO2. After both 5 and 25 min of hypoxia, O2 breathing was associated with transient depressions of ventilation, which were greater after 25 min than after 5 min. Significant depressions were not observed when hyperoxia followed room air breathing, and O2-induced nadirs after hypoxia were lower than those observed during room air breathing. O2 transiently depressed ventilation after hypoxia but not after room air breathing. These results suggest that the normal ventilatory response to isocapnic hypoxia has two components, an excitatory one from peripheral chemoreceptors, which is turned off by O2 breathing, and a slower inhibitory one, probably of central origin, which is affected less promptly by O2 breathing.     

Regional pulmonary blood flow during 96 hours of hypoxia in conscious sheep

The effects of acute hypoxia on regional pulmonary perfusion have been studied previously in anesthetized, artificially ventilated sheep (J. Appl. Physiol. 56: 338-342, 1984). That study indicated that a rise in pulmonary arterial pressure was associated with a shift of pulmonary blood flow toward dorsal (nondependent) areas of the lung. This study examined the relationship between the pulmonary arterial pressor response and regional pulmonary blood flow in five conscious, standing ewes during 96 h of normobaric hypoxia. The sheep were made hypoxic by N2 dilution in an environmental chamber [arterial O2 tension (PaO2) = 37-42 Torr, arterial CO2 tension (PaCO2) = 25-30 Torr]. Regional pulmonary blood flow was calculated by injecting 15-micron radiolabeled microspheres into the superior vena cava during normoxia and at 24-h intervals of hypoxia. Pulmonary arterial pressure increased from 12 Torr during normoxia to 19-22 Torr throughout hypoxia (alpha less than 0.049). Pulmonary blood flow, expressed as %QCO or ml X min-1 X g-1, did not shift among dorsal and ventral regions during hypoxia (alpha greater than 0.25); nor were there interlobar shifts of blood flow (alpha greater than 0.10). These data suggest that conscious, standing sheep do not demonstrate a shift in pulmonary blood flow during 96 h of normobaric hypoxia even though pulmonary arterial pressure rises 7-10 Torr. We question whether global hypoxic pulmonary vasoconstriction is, by itself, beneficial to the sheep.     

Protective Effects of Valproic Acid,a Histone Deacetylase Inhibitor,against Hyperoxic Lung Injury in a Neonatal Rat Model

ObjectiveHistone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury.MethodsForty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O₂ and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated.ResultsVPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFβ3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions.ConclusionsThe present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.     

Increased expression of stress proteins in the surf clam Donax variabilis following hydrogen sulfide exposure

Endogenous free radical production and resulting oxidative damage may result from exposure to hypoxia, hyperoxia, or hydrogen sulfide. Previous investigations of sulfide-induced oxidative damage have produced conflicting results, perhaps because these studies utilized species presumably adapted to sulfide. We examined the effects of sulfide, hypoxia and hyperoxia on the surf clam Donax variabilis to test whether these stressors induce a cellular response to oxidative stress. These clams inhabit high-energy sandy beaches and are unlikely to have specific adaptations to these stressors. In duplicate flow-through experiments performed in fall and spring, clams were exposed to normoxia (22 kPa P(O(2))), hypoxia (10 kPa), hyperoxia (37 kPa), or sulfide with normoxia ( approximately 100 mumol L(-1), 22 kPa respectively) for 24 h. We quantified whole-animal expression of three antioxidants (Cu/Zn and Mn superoxide dismutases, glutathione peroxidase), a lipid peroxidation marker (4-hydroxy-2E-nonenol-adducted protein), a DNA repair enzyme (OGG1-m), four heat shock proteins (small Hsp, Hsp60, Hsp70, and mitochondrial Hsp70), ubiquitin, and actin. Clams exposed to sulfide showed upregulation of the greatest number of stress proteins and the pattern was consistent with a cellular response to oxidative stress. Furthermore, there was a marked seasonality, with greater stress protein expression in clams from the spring.     

支气管肺发育不良小鼠模型的建立

目的建立支气管肺发育不良小鼠模型。方法将30只4日龄雌性昆明小鼠随机分为2组,每组15只,氧气组置于氧箱（FiO20.6）,空气组置于空气中（FiO20.21）,分别于暴露7 d、14 d、21 d时每组随机选取5只,称重后处死,观察肺组织形态学、放射状肺泡计数（radical alveolar counts,RAC）及肺胶原含量变化。结果氧气组各时间点体重较空气组均明显降低（P〈0.001）;实验21 d时氧气组肺组织HE染色下见正常肺泡结构破坏,肺泡隔增厚,肺泡融合;氧气组RAC较空气组显著降低（P〈0.001）;肺胶原天狼猩红特殊染色见Ⅰ型、Ⅲ型胶原增生,较空气组显著增加（P〈0.001）。结论中等浓度氧（FiO20.6）暴露21 d可致小鼠肺发生类似人类支气管肺发育不良改变。     

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude

We tested the hypothesis that exposure of high-altitude (HA) rats to a period of postnatal normoxia has long-term consequences on the ventilatory and hematological acclimatization in adults. Male and female HA rats (3,600 m, Po(2) ? 100 Torr; La Paz, Bolivia) were exposed to normal room air [HA control (HACont)] or enriched oxygen (32% O(2); Po(2) ? 160 Torr) from 1 day before to 15 days after birth [HA postnatal normoxia (HApNorm)]. Hematocrit and hemoglobin values were assessed at 2, 12, and 32 wk of age. Cardiac and lung morphology were assessed at 12 wk by measuring right ventricular hypertrophy (pulmonary hypertension index) and lung air space-to-tissue ratio (indicative of alveolarization). Respiratory parameters under baseline conditions and in response to 32% O(2) for 10 min (relieving the ambient hypoxic stimulus) were measured by whole body plethysmography at 12 wk. Finally, we performed a survival analysis up to 600 days of age. Compared with HACont, HApNorm rats had reduced hematocrit and hemoglobin levels at all ages (both sexes); reduced right ventricular hypertrophy (both sexes); lower air space-to-tissue ratio in the lungs (males only); reduced CO(2) production rate, but higher oxygen uptake (males only); and similar respiratory frequency, tidal volume, and minute ventilation. When breathing 32% O(2), HApNorm male rats had a stronger decrease of minute ventilation than HACont. HApNorm rats had a marked tendency toward longer survival throughout the study. We conclude that exposure to ambient hypoxia during postnatal development in HA rats has deleterious consequences on acclimatization to hypoxia as adults.