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Ventilatory responses to hypoxia and hypercapnia play a vital role in maintaining gas exchange homeostasis and in adaptation to high-altitude environments. This study investigates the mechanisms underlying sensitization of hypoxic and hypercapnic ventilatory response (HVR and HCVR, respectively) in individuals acclimatized to moderate high altitude (3,800 m). Thirty-one participants underwent chemoreflex testing using the Duffin-modified rebreathing technique. Measures were taken at sea level and after 2 days of acclimatization to high altitude. Ventilatory recruitment threshold (VRT), HCVR-Hyperoxia, HCVR-Hypoxia, and HVR were quantified. Acclimatization to high altitude resulted in increased HVR (P < 0.001) and HCVR-Hyperoxia (P < 0.001), as expected. We also observed that the decrease in VRT under hypoxic test conditions significantly contributed to the elevated HVR at high altitude since the change in VRT across hyperoxic and hypoxic test conditions was greater at high altitudes compared to baseline sea-level tests (P = 0.043). Pre-VRT, or basal, ventilation also increased at high altitudes (P < 0.001), but the change did not differ between oxygen conditions. Taken together, these data suggest that the increase in HVR at high altitude is at least partially driven by a larger decrease in the VRT in hypoxia versus hyperoxia at high altitude compared to sea level. This study highlights the intricacies of respiratory adaptations during acclimatization to moderate high altitude, shedding light on the roles of the VRT, baseline respiratory drive, and two-slope HCVR in this process. These findings contribute to our understanding of how human respiratory control responds to hypoxic and hypercapnic challenges at high altitude. NEW & NOTEWORTHY: We report the first measurements of the hypoxic ventilatory response (HVR) after 2 days at high altitude using a CO2 rebreathing technique. We evaluated mechanisms by which the HVR becomes elevated with acclimatization (increased hypercapnic ventilatory response sensitivity in hypoxia, increased baseline respiratory drive in hypoxia, or lower ventilatory recruitment thresholds in hypoxia). For the first time, we report that decreases in the ventilatory recruitment threshold in hypoxia contribute to elevated HVR at high altitude. [ABSTRACT FROM AUTHOR]

Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady‐state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady‐state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady‐state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude‐related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady‐state measurements of resting ventilation (V̇I; L/min), pressure of end‐tidal (PET)CO2 (Torr), and peripheral oxygen saturation (SpO2; %) were measured. A stimulus index (SI; PETCO2/SpO2) was calculated, and SSCD was calculated by indexing V̇I against SI. We found that (a) both V̇I and SSCD increased with ascent to 4240 m (day seven; V̇I: +39%, p < 0.0001, Hedges' g = 1.52; SSCD: +56.%, p < 0.0001, Hedges' g = 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇I: p = 0.02, Hedges' g = 1.04; SSCD: p = 0.02, Hedges' g = 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests. [ABSTRACT FROM AUTHOR]

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a). The time course and magnitude of these integrated acclimatization processes are highly variable between individuals. Using a previously developed metric of renal reactivity (RR), indexing the change in arterial bicarbonate concentration (Δ[HCO3−]a; renal response) over the change in arterial pressure of CO2 (ΔPaCO2; renal stimulus), we aimed to characterize changes in RR magnitude following rapid ascent and residence at altitude. Resident lowlanders (n = 16) were tested at 1,045 m (day [D]0) prior to ascent, on D2 within 24 h of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: PaCO2, [HCO3−]a, and pHa. Compared with D0, PaCO2 and [HCO3−]a were lower on D2 (P < 0.01) and D9 (P < 0.01), whereas significant changes in pHa (P = 0.072) and RR (P = 0.056) were not detected. As pHa appeared fully compensated on D2 and RR did not increase significantly from D2 to D9, these data demonstrate renal acid-base compensation within 24 h at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ΔpHa on D2 and D9 (r ≤ −0.95; P < 0.0001), suggesting that a high-gain renal response better protects pHa. Our study highlights the differential time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization following rapid ascent and residence at high altitude. NEW & NOTEWORTHY We assessed the time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization with rapid ascent and residence at 3,800 m. Despite reductions in PaCO2 upon ascent, pHa was normalized within 24 h of arrival at 3,800 m through renal compensation (i.e., bicarbonate elimination). Renal reactivity (RR) was unchanged between days 2 and 9, suggesting a lack of plasticity at moderate steady-state altitude. RR was strongly correlated with ΔpHa, suggesting that a high-gain renal response better protects pHa. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady‐state cardiorespiratory variables (i.e. hysteresis). Furthermore, we aimed to investigate whether the magnitude of cardiorespiratory hysteresis was associated with the development of acute mountain sickness.What is the main finding and its importance?Hysteresis in steady‐state cardiorespiratory variables quantifies ventilatory acclimatization to high altitude. The magnitude of cardiorespiratory hysteresis during ascent to and descent from high altitude was significantly related to the development of symptoms of acute mountain sickness. Hysteresis in steady‐state chemoreflex drive can provide a simple, non‐invasive method of tracking ventilatory acclimatization to high altitude. Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation‐mediated hypocapnia on steady‐state ventilatory drive. Inter‐individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady‐state cardiorespiratory variables. We hypothesized that: (i) the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii) larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide‐free trekkers ascending to and descending from 5160 m, cardiorespiratory hysteresis was measured in the partial pressure of end‐tidal CO2, peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end‐tidal CO2/peripheral oxygen saturation) and the calculated steady‐state chemoreflex drive (SS‐CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i) ascent–descent hysteresis was present in all cardiorespiratory variables; (ii) SS‐CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii) the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS‐CD hysteresis (rs = −0.408, P = 0.043). We propose that ascent–descent hysteresis is a new and feasible way to quantify ventilatory acclimatization in trekkers during high‐altitude exposure. [ABSTRACT FROM AUTHOR]

Different patterns of hypoxia evoke different forms of plasticity in the neural control of ventilation. For example, acute intermittent hypoxia produces long term facilitation (LTF) of ventilation, while chronic sustained hypoxia (CH) causes ventilatory acclimatization to hypoxia (VAH). In both LTF and VAH, ventilation in normoxia is greater than normal after the hypoxic stimulus is removed and the acute hypoxic ventilatory response can increase. However, the mechanisms of LTF and VAH are thought to be different based on previous results showing serotonin 5HT2 receptors, which are G protein coupled receptors (GPCR) that activate GQ signaling, contribute to LTF but not VAH. Newer results show that a different GPCR, namely adenosine A2A receptors and the GS signaling pathway, cause LTF with more severe intermittent hypoxia, i.e., PaO2 = 25–30 Torr for GS versus 35–45 Torr for LTF with the GQ signaling pathway. We hypothesized adenosine A2A receptors and GS signaling are involved in establishing VAH with longer term moderate CH and tested this in adult male rats by measuring ventilatory responses to O2 and CO2 with barometric pressure plethysmography after administering MSX-3 or ketanserin (A2A and 5HT2 antagonists, respectively, both 1 mg/Kg i.p.) during CH for 7 days. Blocking GS or GQ signals throughout CH exposure, significantly decreased VAH. After VAH was established, GQ blockade did not affect ventilation while GS blockade increased VAH. Similar to LTF, data support roles for both GQ and GS pathways in the development of VAH but after VAH has been established, the GS pathway inhibits VAH.

Exposure to chronic sustained hypoxia (SH), as experienced in high altitudes, elicits an increase in ventilation, named ventilatory acclimatization to hypoxia (VAH). We previously showed that rats exposed to short-term (24 h) SH exhibit enhanced abdominal expiratory motor activity at rest, accompanied by augmented baseline sympathetic vasoconstrictor activity. In the present study, we investigated whether the respiratory and sympathetic changes elicited by short-term SH are accompanied by carotid body chemoreceptor sensitization. Juvenile male Holtzman rats (60–80 g) were exposed to SH (10% O2 for 24 h) or normoxia (control) to examine basal and hypoxic-induced ventilatory parameters in unanesthetized conditions, as well as the sensory response of carotid body chemoreceptors in artificially perfused in situ preparations. Under resting conditions (normoxia/normocapnia), SH rats (n = 12) exhibited higher baseline respiratory frequency, tidal volume, and minute ventilation compared to controls (n = 11, P < 0.05). SH group also showed greater hypoxia ventilatory response than control group (P < 0.05). The in situ preparations of SH rats (n = 8) exhibited augmented baseline expiratory and sympathetic activities under normocapnia, with additional bursts in abdominal and thoracic sympathetic nerves during late expiratory phase that were not seen in controls (n = 8, P < 0.05). Interestingly, basal and potassium cyanide-induced afferent activity of carotid sinus nerve (CSN) was similar between SH and control rats. Our findings indicate that the maintenance of elevated resting ventilation, baseline sympathetic overactivity, and enhanced ventilatory responses to hypoxia in rats exposed to 24 h of SH are not dependent on increased basal and sensorial activity of carotid body chemoreceptors.

Different patterns of hypoxia evoke different forms of plasticity in the neural control of ventilation. For example, acute intermittent hypoxia produces long term facilitation (LTF) of ventilation, while chronic sustained hypoxia (CH) causes ventilatory acclimatization to hypoxia (VAH). In both LTF and VAH, ventilation in normoxia is greater than normal after the hypoxic stimulus is removed and the acute hypoxic ventilatory response can increase. However, the mechanisms of LTF and VAH are thought to be different based on previous results showing serotonin 5HT2 receptors, which are G protein coupled receptors (GPCR) that activate GQ signaling, contribute to LTF but not VAH. Newer results show that a different GPCR, namely adenosine A2A receptors and the GS signaling pathway, cause LTF with more severe intermittent hypoxia, i.e., PaO2 = 25–30 Torr for GS versus 35–45 Torr for LTF with the GQ signaling pathway. We hypothesized adenosine A2A receptors and GS signaling are involved in establishing VAH with longer term moderate CH and tested this in adult male rats by measuring ventilatory responses to O2 and CO2 with barometric pressure plethysmography after administering MSX-3 or ketanserin (A2A and 5HT2 antagonists, respectively, both 1 mg/Kg i.p.) during CH for 7 days. Blocking GS or GQ signals throughout CH exposure, significantly decreased VAH. After VAH was established, GQ blockade did not affect ventilation while GS blockade increased VAH. Similar to LTF, data support roles for both GQ and GS pathways in the development of VAH but after VAH has been established, the GS pathway inhibits VAH. [ABSTRACT FROM AUTHOR]

Exposure to chronic sustained hypoxia (SH), as experienced in high altitudes, elicits an increase in ventilation, named ventilatory acclimatization to hypoxia (VAH). We previously showed that rats exposed to short-term(24 h) SH exhibit enhanced abdominal expiratory motor activity at rest, accompanied by augmented baseline sympathetic vasoconstrictor activity. In the present study, we investigated whether the respiratory and sympathetic changes elicited by short-term SH are accompanied by carotid body chemoreceptor sensitization. Juvenile male Holtzman rats (60-80 g) were exposed to SH (10% O2 for 24 h) or normoxia (control) to examine basal and hypoxic-induced ventilatory parameters in unanesthetized conditions, as well as the sensory response of carotid body chemoreceptors in artificially perfused in situ preparations. Under resting conditions (normoxia/normocapnia), SH rats (n = 12) exhibited higher baseline respiratory frequency, tidal volume, and minute ventilation compared to controls (n = 11, P < 0.05). SH group also showed greater hypoxia ventilatory response than control group (P < 0.05). The in situ preparations of SH rats (n = 8) exhibited augmented baseline expiratory and sympathetic activities under normocapnia, with additional bursts in abdominal and thoracic sympathetic nerves during late expiratory phase that were not seen in controls (n = 8, P < 0.05). Interestingly, basal and potassium cyanide-induced afferent activity of carotid sinus nerve (CSN) was similar between SH and control rats. Our findings indicate that the maintenance of elevated resting ventilation, baseline sympathetic overactivity, and enhanced ventilatory responses to hypoxia in rats exposed to 24 h of SH are not dependent on increased basal and sensorial activity of carotid body chemoreceptors. [ABSTRACT FROM AUTHOR]

Patients with obstructive sleep apnea (OSA) show augmented ventilatory, sympathetic and cardiovascular responses to hypoxia. The facilitatory effect of chronic intermittent hypoxia (CIH) on the hypoxic ventilatory response has been attributed to a potentiation of the carotid body (CB) chemosensory response to hypoxia. However, it is a matter of debate whether the effects induced by CIH on ventilatory responses to hypoxia are due to an enhanced CB activity. Recently, we studied the effects of short cyclic hypoxic episodes on cat cardiorespiratory reflexes, heart rate variability, and CB chemosensory activity. Cats were exposed to cyclic hypoxic episodes repeated during 8 hours for 4 days. Our results showed that CIH selectively enhanced ventilatory and carotid chemosensory responses to acute hypoxia. Exposure to CIH did not increase basal arterial pressure, heart rate, or their changes induced by acute hypoxia. However, the spectral analysis of heart rate variability of CIH cats showed a marked increase of the low/high frequency ratio and an increased variability in the low frequency band of heart rate variability, similar to what is observed in OSA patients. Thus, it is likely that the enhanced CB reactivity to hypoxia may contribute to the augmented ventilatory response to hypoxia.

While a number of published studies exist to guide endurance athletes with the best practices regarding implementation of altitude training, a key unanswered question concerns the proper timing of return to sea level prior to major competitions. Evidence reviewed here suggests that, altogether, the deacclimatization responses of hematological, ventilatory, and biomechanical factors with return to sea level likely interact to determine the best timing for competitive performance. [ABSTRACT FROM AUTHOR]

There is an expectation that repeated daily exposures to normobaric hypoxia (NH) will induce ventilatory acclimatization and lessen acute mountain sickness (AMS) and the exercise performance decrement during subsequent hypobaric hypoxia (HH) exposure. However, this notion has not been tested objectively. Healthy, unacclimatized sea-level (SL) residents slept for 7.5 h each night for 7 consecutive nights in hypoxia rooms under NH [n = 14, 24 ± 5 (SD) yr] or "sham" (n = 9, 25 ± 6 yr) conditions. The ambient percent O2 for the NH group was progressively reduced by 0.3% [150 m equivalent (equiv)] each night from 16.2% (2,200 m equiv) on night 1 to 14.4% (3,100 m equiv) on night 7, while that for the ventilatory- and exercise-matched sham group remained at 20.9%. Beginning at 25 h after sham or NH treatment, all subjects ascended and lived for 5 days at HH (4,300 m). End-tidal Pco2, O2 saturation (SaO2), AMS, and heart rate were measured repeatedly during daytime rest, sleep, or exercise (11.3-km treadmill time trial). From pre- to posttreatment at SL, resting end-tidal Pco2 decreased (P < 0.01) for the NH (from 39 ± 3 to 35 ± 3 mmHg), but not for the sham (from 39 ± 2 to 38 ± 3 mmHg), group. Throughout HH, only sleep SaO2 was higher (80 ± 1 vs. 76 ± 1%, P < 0.05) and only AMS upon awakening was lower (0.34 ± 0.12 vs. 0.83 ± 0.14, P < 0.02) in the NH than the sham group; no other between-group rest, sleep, or exercise differences were observed at HH. These results indicate that the ventilatory acclimatization induced by NH sleep was primarily expressed during HH sleep. Under HH conditions, the higher sleep SaO2 may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise performance for the remainder of each day. [ABSTRACT FROM AUTHOR]

Abstract: Highland natives show unique breathing patterns and ventilatory responses at altitude, both at rest and during exercise. For many ventilatory traits, there is also significant variation between highland native groups, including indigenous populations in the Andes and Himalaya, and more recent altitude arrivals in places like Colorado. This review summarizes the literature in this area with some focus on partitioning putative population genetic differences from differences acquired through lifelong exposure to hypoxia. Current studies suggest that Tibetans have high resting ventilation , and a high hypoxic ventilatory response (HVR), similar to altitude acclimatized lowlanders. Andeans, in contrast, show low resting and a low or “blunted” HVR, with little evidence that these traits are acquired via lifelong exposure. Resting of non-indigenous altitude natives is not well documented, but lifelong hypoxic exposure almost certainly blunts HVR in these groups through decreased chemosensitivity to hypoxia in a process known as hypoxic desensitization (HD). Together, these studies suggest that the time course of ventilatory response, and in particular the origin or absence of HD, depends on population genetic background i.e., the allele or haplotype frequencies that characterize a particular population. During exercise, altitude natives have lower compared to acclimatized lowland controls. Altitude natives also have smaller alveolar-arterial partial pressure differences during exercise suggesting differences in gas exchange efficiency. Small in highland natives of Colorado underscores the likely importance of developmental adaptation to hypoxia affecting structural/functional aspects of gas exchange with resultant changes in breathing pattern. However, in Andeans, at least, there is also evidence that low exercise is determined by genetic background affecting ventilatory control independent of gas exchange. Additional studies are needed to elucidate the effects of gene, environment, and gene-environment interaction on these traits, and these effects are likely to differ widely between altitude native populations. [Copyright &y& Elsevier]

Abstract: Carotid body chemoreceptors are essential for time-dependent changes in ventilatory control during chronic hypoxia. Early theories of ventilatory acclimatization to hypoxia focused on time-dependent changes in known ventilatory stimuli, such as small changes in arterial pH that may play a significant role in some species. However, plasticity in the cellular and molecular mechanisms of carotid body chemoreception play a major role in ventilatory acclimatization to hypoxia in all species studied. Chronic hypoxia causes changes in (a) ion channels (potassium, sodium, calcium) to increase glomus cell excitability, and (b) neurotransmitters (dopamine, acetylcholine, ATP) and neuromodulators (endothelin-1) to increase carotid body afferent activity for a given and optimize O2-sensitivity. O2-sensing heme-containing molecules in the carotid body have not been studied in chronic hypoxia. Plasticity in medullary respiratory centers processing carotid body afferent input also contributes to ventilatory acclimatization to hypoxia. It is not known if the same mechanisms occur in patients with chronic hypoxemia from lung disease or high altitude natives. [Copyright &y& Elsevier]

Abstract: Adult rats have decreased carotid body volume and reduced carotid sinus nerve, phrenic nerve, and ventilatory responses to acute hypoxic stimulation after exposure to postnatal hyperoxia (60% O2, PNH) during the first 4 weeks of life. Moreover, sustained hypoxic exposure (12%, 7 days) partially reverses functional impairment of the acute hypoxic phrenic nerve response in these rats. Similarly, 2 weeks of PNH results in the same phenomena as above except that ventilatory responses to acute hypoxia have not been measured in awake rats. Thus, we hypothesized that 2-week PNH-treated rats would also exhibit blunted chemoafferent responses to acute hypoxia, but would exhibit ventilatory acclimatization to sustained hypoxia. Rats were born into, and exposed to PNH for 2 weeks, followed by chronic room-air exposure. At 3–4 months of age, two studies were performed to assess: (1) carotid sinus nerve responses to asphyxia and sodium cyanide in anesthetized rats and (2) ventilatory and blood gas responses in awake rats before (d0), during (d1 and d7), and 1 day following (d8) sustained hypoxia. Carotid sinus nerve responses to i.v. NaCN and asphyxia (10s) were significantly reduced in PNH-treated versus control rats; however, neither the acute hypoxic ventilatory response nor the time course or magnitude of ventilatory acclimatization differed between PNH and control rats despite similar levels of . Although carotid body volume was reduced in PNH rats, carotid body volumes increased during sustained hypoxia in both PNH and control rats. We conclude that normal acute and chronic ventilatory responses are related to retained (though impaired) carotid body chemoafferent function combined with central neural mechanisms which may include brainstem hypoxia-sensitive neurons and/or brainstem integrative plasticity relating both central and peripheral inputs. [Copyright &y& Elsevier]

Abstract: To determine if laboratory strains of guinea pigs bred at sea level (SL) are “pre-adapted” to high altitude (HA), we raised litter-matched weanling Hartley guinea pigs for 4 months at SL, intermediate altitude (IA, 1250m) or HA (3800m) and exposed them acutely to 100, 21 and 12% inspired O2 at their respective altitude of residence. Control animals raised at SL were also exposed acutely to 10 and 8% inspired O2. In awake spontaneously breathing guinea pigs raised at SL, resting minute ventilation and tidal volume increased significantly when inspired O2 tension fell below about 60mmHg. In guinea pigs raised at IA or HA, ventilation was higher at any given inspired O2 tension in direct relationship to the altitude of residence. Resting hematocrit was also higher in animals raised at HA than at SL. We conclude that the pattern of ventilatory acclimatization to HA exposure in Hartley guinea pigs is similar to that in laboratory rats and human lowlanders; therefore laboratory guinea pigs are not pre-adapted and are suitable animals for the study of adaptation to high altitude. [Copyright &y& Elsevier]

Abstract: Developmental hyperoxia impairs carotid chemoreceptor development and induces long-lasting reduction in carotid sinus nerve (CSN) responses to hypoxia in adult rats. Studies were carried out to determine if CSN responses to acute hypoxia would exhibit hypoxia-induced plasticity in adult 3–5-months-old rats previously treated with postnatal hyperoxia (60% O2, PNH) of 1, 2, or 4 weeks duration. CSN responses to acute hypoxia were assessed in adult rats exposed to 1 week of sustained hypoxia (12% O2, SH). In normal adult rats and adult rats treated with 1 week of PNH, CSN responses to acute hypoxia were significantly increased in urethane-anesthetized rats when studied 3–5h after SH. Apparent increases in CSN responses to hypoxia were not significant in rats treated with 2 weeks of PNH and were clearly absent after 4 weeks of PNH, but exponential analysis suggests a PNH duration-dependent plasticity of the CSN response to acute hypoxia after SH. In a second study rats exposed to 2 weeks of PNH were treated with SH for 1 week as adults and acute hypoxic responses were tested 4–5 months later. CSN responses in these rats were unaffected by SH suggesting a lack of persistent SH-induced functional plasticity. We conclude that rats treated with 1 week of PNH retain the capacity for hypoxia-induced plasticity of carotid chemoafferent function and some potential for plasticity may be present after 2 weeks of PNH, whereas 4 weeks of PNH impairs the capability of rats to exhibit plasticity following 1 week of SH. [Copyright &y& Elsevier]