Changes in ventilatory adaptations associated with long-term intermittent hypoxia across the age spectrum in the rat

Intermittent hypoxia (IH) induces alterations in respiratory control that reflect various types of ventilatory plasticity. In freely behaving rats, acute exposure to IH elicits enhancements in normoxic minute ventilation (VE), termed ventilatory long-term facilitation. Exposure to longer time periods of IH induces unique ventilatory adaptations to intermittent hypoxia (VAIH). We hypothesized that long-term IH-induced ventilatory plasticity may be developmentally regulated and thus, IH exposures at progressively later post-natal ages may elicit differential effects on the magnitude of VAIH. To examine this issue, male Sprague-Dawley rats were exposed to 30 continuous days of IH beginning at post-natal ages 1, 10, 30, 60, 180, 360, and 540 days. Control animals were exposed to normoxic conditions with room air. Normoxic VE was significantly higher in IH-exposed rats (p < 0.01) except for the group in which IH was initiated at post-natal age 540 days (p = NS). The magnitude of VAIH was greatest in rats exposed in the immediate post-natal period and gradually diminished with advancing post-natal age. Enhanced normoxic VE was due to significant contributions from both frequency (p < 0.01) and tidal volume (p < 0.01), and could not be accounted for by changes in metabolic rate. We conclude that the magnitude of IH-induced ventilatory plasticity is age-dependent with progressive declines becoming apparent with advancing post-natal age.