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The purpose of this article is to set out the hypothesis that arterial PO2 may play a significant role in the regulation of breathing at sea level. The following points are made: 1) Although CO2 is clearly the dominant feedback signal in the acute setting, there is evidence, particularly clinical observation, that the ventilatory response to CO2 may adapt. 2) Although the ventilatory response to an acute variation in alveolar PO2 around sea-level values is feeble, studies at altitude have shown that over longer-time periods alveolar PO2 is a more powerful regulator of ventilation. 3) Recent evidence suggests that mechanisms associated with ventilatory acclimatization to hypoxia are active at sea-level values for PO2, and indeed affect the acute ventilatory response to hypoxia. 4) While most evidence suggests that the peripheral and central chemoreflexes are independent and additive in their contributions to ventilation, experiments over longer durations suggest that peripheral chemoreceptor afferents may play an important role in regulating central chemoreflex sensitivity to CO2. This is potentially an important mechanism by which oxygen can alter the acute chemoreflex responses to CO2. In conclusion, the mechanisms underlying ventilatory acclimatization to hypoxia may have an important role in regulating the respiratory system at sea level.

Original publication




Journal article


Adv Exp Med Biol

Publication Date





339 - 348


Acclimatization, Altitude, Animals, Carbon Dioxide, Humans, Hypoxia, Oceans and Seas, Oxygen, Respiration, Ventilation