Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2 : role of carotid body CO2.

We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2 . The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body PCO2 ≈ 22, 41 and 68 mmHg, respectively) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly-isolated and extracorporeally-perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB-denervated dogs, absence of hyper-/hypoventilatory responses to CB perfusion with PCO2 of 19-75 mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO2 response slopes were increased 303% for minute ventilation (V̇I)(P ≤ 0.01) and 251% for mean inspiratory flow rate (VT /TI ) (P ≤ 0.05) when the CB was hypercapnic vs. hypocapnic; central CO2 response slopes for tidal volume (VT ), breathing frequency (fb ) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO2 response slopes were also increased 237% for V̇I(P ≤ 0.01) and 249% for VT /TI (P ≤ 0.05) when the CB was normocapnic vs. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper-/hypocapnia agree with previous findings using CB hyper-/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O2 and/or CO2 .