Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia

David De La Zerda, J. A. Stokes, J. Do, A. Go, Z. Fu, F. L. Powell

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, PiO2 =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O2 and CO2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia.

Original languageEnglish (US)
JournalRespiratory Physiology and Neurobiology
DOIs
StateAccepted/In press - 2017

Fingerprint

Ibuprofen
Acclimatization
Microglia
Solitary Nucleus
Astrocytes
Respiratory Center
Hypoxia
Ventilation
Anti-Inflammatory Agents
Gases
Immunohistochemistry
Maintenance

Keywords

  • Astrocyte
  • Hypoxic ventilatory response
  • Inflammation
  • Microglia
  • Non-steroidal anti-inflammatory drug (NSAID)
  • Nucleus tractus solitarii
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

Cite this

Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia. / De La Zerda, David; Stokes, J. A.; Do, J.; Go, A.; Fu, Z.; Powell, F. L.

In: Respiratory Physiology and Neurobiology, 2017.

Research output: Contribution to journalArticle

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AU - Fu, Z.

AU - Powell, F. L.

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N2 - Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, PiO2 =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O2 and CO2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia.

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