Oxygen sensitivity of central cardiorespiratory regions

It has been known for more than a century that respiration is stimulated by hypoxia. In 1868 Pflüger (1) demonstrated that ventilation increased when dogs inhaled nitrogen. Prior to identification of the hypoxia-sensitive carotid chemoreceptors in 1930 (2), the most commonly held theory was that the respiratory centers themselves were sensitive to hypoxia, presumably by an indirect effect on “central acidity” (2a,2b,3,4). Identification of the carotid and aortic chemoreceptors in 1930 by Heymans and colleagues (2) and the demonstration that, in the absence of intact carotid sinus and aortic depressor nerves, inhalation of nitrogen resulted in only a slight stimulation of respiration represented a major breakthrough in understanding the reflex stimulation of respiration by chemical stimuli, and effectively ended the search for a central oxygen sensor. Interest in identifying central sites of oxygen chemosensitivity shifted toward elucidating the mechanism of oxygen transduction by the carotid body chemoreceptors.