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

Abstract

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 .

Figure 1

Breath-by-breath time course plots showing the effects of hypercapnic and hypocapnic CB perfusion on ventilation and the ventilatory response to systemic hypercapnia in two representative dogs Key transitions are marked by vertical dashed lines; the initiation of perfusion is indicated by a filled arrow. , and for each condition are indicated above each panel. Dog W (upper panels) showed limited response to CB hypo- or hypercapnic perfusion during air breathing. Dog X (lower panels) showed larger responses to CB hypo- or hypercapnic perfusion during air breathing. Note that in both dogs,(a) there was a transient hyper-or hypoventilation in response to CB hypercapnia and CB hypocapnia, respectively (filled arrow and vertical dashed line),(b) after the transient peak or nadir, partial ventilatory compensation occurred (between first two vertical dashed lines in each panel), and(c) the ventilatory responses to increased and systemic hypercapnia (last 3 sections in each panel) were greater in both dogs during CB hypercapnia vs. CB hypocapnia (compare right panel to left panel in each dog after the filled arrow and vertical dashed line).

Figure 2

Steady-state ventilatory responses of five key ventilatory components to increased FICO₂ Data obtained during CB normocapnic ( = 39.2 mmHg), CB hypercapnic ( = 73.4 mmHg) and CB hypocapnic ( = 22.3 mmHg) perfusion in a representative dog. Lines are linear regressions.

Figure 3

Individual and mean ventilatory response slopes to increased systemic PaCO₂ grouped by CB perfusate condition Each type of symbol represents the responses of one dog; the thick horizontal bars represent the group means; vertical dashed arrows represent ±95% confidence interval. *Mean value significantly different (*P ≤ 0.05; **P ≤ 0.01) from hypocapnic mean; ^†significantly different (^†P ≤ 0.05; ^††P ≤ 0.01) from normocapnic mean. Some symbols have been moved to the left where extensive overlap between points occurred. n = 7 for CB hypocapnia ( = 22.3 ± 2.9 mmHg) and CB hypercapnia ( = 68.2 ± 8.3 mmHg), n = 6 for CB normocapnia ( = 41.1 ± 6.1 mmHg). (See text for details.)

Figure 4

Ventilatory responses of to increased Fico₂ during CB hypercapnic and CB hypocapnic perfusion for each of the seven dogs Regression equations and r² values are adjacent to the regression line they pertain to. (See text for details.)

Figure 5

Ventilatory responses of V_T to increased Fico₂ during CB hypercapnic and CB hypocapnic perfusion for each of the seven dogs Regression equations and r² values are adjacent to the regression line they pertain to (See text for details). Symbols as in Figure 4.

Figure 6

Ventilatory responses of f_b to increased Fico₂ during CB hypercapnic and CB hypocapnic perfusion for each of the seven dogs Regression equations and r² values are adjacent to the regression line they pertain to (See text for details). Symbols as in Figure 4.

Figure 7

Ventilatory responses of V_T/T_I to increased Fico₂ during CB hypercapnic and CB hypocapnic perfusion for each of the seven dogs Regression equations and r² values are adjacent to the regression line they pertain to (See text for details). Symbols as in Figure 4.

Figure 8

Ventilatory responses of DiRR to increased Fico₂ during CB hypercapnic and CB hypocapnic perfusion for each of the seven dogs Regression equations and r² values are adjacent to the regression line they pertain to (See text for details). Symbols as in Figure 4.