Contributions of central and peripheral chemoreceptors to the ventilatory response to CO2/H+

Abstract

The major objective of this review is to evaluate existing information and reach conclusions regarding whether there is interaction between P(CO(2))/H(+) stimulation of carotid (peripheral) and intracranial (central) chemoreceptors. Interaction is defined as a ventilatory response to simultaneous changes in the degree of Pco2/H(+) stimulation of both chemoreceptors that is greater (hyperadditive) or less (hypoadditive) than the sum of the responses when stimulation of each set of chemoreceptors is individually altered. Simple summation of the simultaneous changes in stimuli results in no interaction (i.e., additive interaction). Knowledge of the nature of central/peripheral interaction is crucial for determining the physiological significance of newer models of ventilatory control based on recent neuroanatomic observations of the circuitry of key elements of the ventilatory control system. In this review, we will propose that these two sets of receptors are not functionally separate but rather that they are dependent on one another such that the sensitivity of the medullary chemoreceptors is critically determined by input from the peripheral chemoreceptors and possibly other breathing-related reflex afferents as well. The short format of this minireview demands that we be somewhat selective in developing our ideas. We will briefly discuss the limitations of experiments used to study CO(2)/H(+) sensitivity and interaction to date, traditional views of the relative contributions of peripheral and central chemoreceptors to CO(2)/H(+) sensitivity, the evidence for and against different types of interaction, and the effect of tonic carotid chemoreceptor afferent activity on central control mechanisms.

Fig. 1.

Goats hypoventilate and have reduced sensitivity to CO₂ for at least 7 days after carotid body denervation (CBD), but thereafter, there is a normalization of breathing. Depicted are data from a single, awake goat and on each day data were obtained while breathing room air (initial point) and while inhaling in order 3, 5, and 7% CO₂ gas mixtures. Note the reduced ventilation and increased arterial Pco2 (Pa_CO2) in eupnea and the reduced ventilatory response slope over the first 7 days after CBD. Data are from Ref. . V̇i, inspired pulmonary ventilation.

Fig. 2.

A: breath-by-breath V̇i from one trial of carotid body (CB) chemoreceptor inhibition via hyperoxia and hypocapnia. Inhibition begins at time 0 (vertical line). Note the initial 60% decrease in ventilation followed by only partial compensation to the hypoventilation-induced respiratory acidosis. B: bar graph of the time course of ventilation during CB chemoreceptor inhibition. Data are normalized to control (where control is normal, endogenous CB perfusion, i.e., CB not inhibited) and presented as means ± SD. Control is arbitrarily set to zero to more clearly indicate the direction of change. “1st Change” represents the first V̇i response > 3 SDs below the control mean. “Nadir” represents the 3-breath mean consisting of the breath with the lowest V̇i and the preceding and subsequent breaths. “Steady-state” represents the mean values of the first 3 consecutive breaths within 1 SD of the mean V̇i from the last 30 s of the experiment (> 7 min of perfusion). “5 min” represents the mean ventilatory values of the last 30 s of the 5th minute of CB inhibition. “End” represents the mean ventilatory values from the last 30 s of each experiment regardless of duration. Times in the bottom of each bar denote the average time for that response. Note that the nadir ventilatory response to CB inhibition averaged 60% below control and the maintained steady-state response was 38% below control. *Significant difference from control values, P < 0.05. Data are from Ref. .