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Ibuprofen blocks time-dependent increases in hypoxic ventilation in rats.

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  • 1Division of Physiology, Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0623, United States.

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Inflammation increases carotid body oxygen sensitivity during chronic hypoxia. Blocking inflammation with ibuprofen reduced this response and ventilatory acclimatization in rats, suggesting a role for inflammatory pathways.

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Area of Science:

  • Physiology
  • Neuroscience
  • Immunology

Background:

  • Inflammatory processes are implicated in carotid body O(2) sensitivity during chronic hypoxia.
  • Immune cell invasion and inflammatory cytokine expression increase in the carotid body under chronic hypoxic conditions.

Purpose of the Study:

  • To investigate if blocking inflammation with ibuprofen attenuates ventilatory acclimatization to hypoxia.
  • To determine if ibuprofen affects carotid body O(2) sensitivity during chronic hypoxia.

Main Methods:

  • Conscious rats were acclimatized to hypoxia (10% O(2)) for 7 days.
  • Rats received daily intraperitoneal injections of ibuprofen (4mg/kg) or saline.
  • Ventilation and inflammatory cytokine levels (IL-1β, IL-6) in the brainstem were measured.

Main Results:

  • Ibuprofen administration blocked the typical increase in hypoxic ventilation observed in saline-treated chronically hypoxic rats.
  • Ibuprofen had no effect on ventilation in normoxic control rats.
  • Ibuprofen treatment prevented the hypoxia-induced increases in IL-1β and IL-6 in the brainstem.

Conclusions:

  • Blocking inflammation with ibuprofen reduces ventilatory acclimatization to hypoxia in rats.
  • These findings support the hypothesis that inflammatory processes contribute to increased carotid body O(2) sensitivity during chronic hypoxia.
  • Inflammatory pathways in both the carotid body and the central nervous system appear to play a role in hypoxic ventilatory acclimatization.