title: Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia.
abstract: Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2(Control) or 60% O2(Hyperoxia) until studied at 4, 6-7, or 13-14days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2at all ages; CO2sensitivity recovered within 7days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS.
authors.affiliation: Department of Biology, Bates College, Lewiston, ME, USA. Electronic address: rbavis@bates.edu.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Bavis
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, OH, USA.
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Li
authors.affiliation: Department of Biology, Bates College, Lewiston, ME, USA.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: DeAngelis
authors.affiliation: Department of Biology, Bates College, Lewiston, ME, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: March
authors.affiliation: Department of Biology, Bates College, Lewiston, ME, USA.
authors.forename: Josefine A
authors.initials: JA
authors.lastname: Wallace
authors.affiliation: Department of Biology, Bates College, Lewiston, ME, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Logan
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, OH, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Putnam
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D002344:Carotid Body / Q000254:growth & development / Q000473:pathology*; D002628:Chemoreceptor Cells / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology*; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D012123:Pulmonary Ventilation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D002245:Carbon Dioxide; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline
keywords: Carotid body; Central chemoreceptor; Developmental plasticity; Hypercapnic ventilatory response; Nucleus tractus solitarius