Ventilatory and carotid body responses to acute hypoxia in rats exposed to chronic hypoxia during the first and second postnatal weeks

•Rats were exposed to chronic hypoxia (CH) for the first or second postnatal week.•CH blunted the hypoxic ventilatory response (HVR) in both age groups.•The blunted HVR was associated with diminished carotid body O2 sensitivity.•CH during the first (but not second) week delayed maturation of the bip...

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Veröffentlicht in:Respiratory physiology & neurobiology 2020-04, Vol.275, p.103400-103400, Article 103400
Hauptverfasser: Bavis, Ryan W., Song, Monata J., Smachlo, Julia P., Hulse, Alexander, Kenison, Holli R., Peralta, Jose N., Place, Jennifer T., Triebwasser, Sam, Warden, Sarah E., McDonough, Amy B.
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container_title Respiratory physiology & neurobiology
container_volume 275
creator Bavis, Ryan W.
Song, Monata J.
Smachlo, Julia P.
Hulse, Alexander
Kenison, Holli R.
Peralta, Jose N.
Place, Jennifer T.
Triebwasser, Sam
Warden, Sarah E.
McDonough, Amy B.
description •Rats were exposed to chronic hypoxia (CH) for the first or second postnatal week.•CH blunted the hypoxic ventilatory response (HVR) in both age groups.•The blunted HVR was associated with diminished carotid body O2 sensitivity.•CH during the first (but not second) week delayed maturation of the biphasic HVR.•The anti-inflammatory drug ibuprofen did not block this respiratory plasticity. Chronic hypoxia (CH) during postnatal development causes a blunted hypoxic ventilatory response (HVR) in neonatal mammals. The magnitude of the HVR generally increases with age, so CH could blunt the HVR by delaying this process. Accordingly, we predicted that CH would have different effects on the respiratory control of neonatal rats if initiated at birth versus initiated later in postnatal development (i.e., after the HVR has had time to mature). Rats had blunted ventilatory and carotid body responses to hypoxia whether CH (12 % O2) occurred for the first postnatal week (P0 to P7) or second postnatal week (P7 to P14). However, if initiated at P0, CH also caused the HVR to retain the “biphasic” shape characteristic of newborn mammals; CH during the second postnatal week did not result in a biphasic HVR. CH from birth delayed the transition from a biphasic HVR to a sustained HVR until at least P9–11, but the HVR attained a sustained (albeit blunted) phenotype by P13–15. Since delayed maturation of the HVR did not completely explain the blunted HVR, we tested the alternative hypothesis that the blunted HVR was caused by an inflammatory response to CH. Daily administration of the anti-inflammatory drug ibuprofen (4 mg kg−1, i.p.) did not alter the effects of CH on the HVR. Collectively, these data suggest that CH blunts the HVR in neonatal rats by impairing carotid body responses to hypoxia and by delaying (but not preventing) postnatal maturation of the biphasic HVR. The mechanisms underlying this plasticity require further investigation.
doi_str_mv 10.1016/j.resp.2020.103400
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Chronic hypoxia (CH) during postnatal development causes a blunted hypoxic ventilatory response (HVR) in neonatal mammals. The magnitude of the HVR generally increases with age, so CH could blunt the HVR by delaying this process. Accordingly, we predicted that CH would have different effects on the respiratory control of neonatal rats if initiated at birth versus initiated later in postnatal development (i.e., after the HVR has had time to mature). Rats had blunted ventilatory and carotid body responses to hypoxia whether CH (12 % O2) occurred for the first postnatal week (P0 to P7) or second postnatal week (P7 to P14). However, if initiated at P0, CH also caused the HVR to retain the “biphasic” shape characteristic of newborn mammals; CH during the second postnatal week did not result in a biphasic HVR. CH from birth delayed the transition from a biphasic HVR to a sustained HVR until at least P9–11, but the HVR attained a sustained (albeit blunted) phenotype by P13–15. Since delayed maturation of the HVR did not completely explain the blunted HVR, we tested the alternative hypothesis that the blunted HVR was caused by an inflammatory response to CH. Daily administration of the anti-inflammatory drug ibuprofen (4 mg kg−1, i.p.) did not alter the effects of CH on the HVR. Collectively, these data suggest that CH blunts the HVR in neonatal rats by impairing carotid body responses to hypoxia and by delaying (but not preventing) postnatal maturation of the biphasic HVR. 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Since delayed maturation of the HVR did not completely explain the blunted HVR, we tested the alternative hypothesis that the blunted HVR was caused by an inflammatory response to CH. Daily administration of the anti-inflammatory drug ibuprofen (4 mg kg−1, i.p.) did not alter the effects of CH on the HVR. Collectively, these data suggest that CH blunts the HVR in neonatal rats by impairing carotid body responses to hypoxia and by delaying (but not preventing) postnatal maturation of the biphasic HVR. 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Chronic hypoxia (CH) during postnatal development causes a blunted hypoxic ventilatory response (HVR) in neonatal mammals. The magnitude of the HVR generally increases with age, so CH could blunt the HVR by delaying this process. Accordingly, we predicted that CH would have different effects on the respiratory control of neonatal rats if initiated at birth versus initiated later in postnatal development (i.e., after the HVR has had time to mature). Rats had blunted ventilatory and carotid body responses to hypoxia whether CH (12 % O2) occurred for the first postnatal week (P0 to P7) or second postnatal week (P7 to P14). However, if initiated at P0, CH also caused the HVR to retain the “biphasic” shape characteristic of newborn mammals; CH during the second postnatal week did not result in a biphasic HVR. CH from birth delayed the transition from a biphasic HVR to a sustained HVR until at least P9–11, but the HVR attained a sustained (albeit blunted) phenotype by P13–15. 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1878-1519
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Age Factors
Animals
Animals, Newborn
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Carotid body
Carotid Body - physiopathology
Control of breathing
Developmental plasticity
Female
Hypoxia - physiopathology
Hypoxic ventilatory response
Ibuprofen - pharmacology
Inflammation
Inflammation - drug therapy
Pregnancy
Rats
Rats, Sprague-Dawley
Respiration
Sustained hypoxia
title Ventilatory and carotid body responses to acute hypoxia in rats exposed to chronic hypoxia during the first and second postnatal weeks
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