Effects of domperidone on neonatal and adult carotid chemoreceptors in the cat

It has been postulated that the weak carotid chemoreceptor responses of neonatal mammals may be due to inhibition produced by high levels of endogenous dopamine release or exaggerated sensitivity to dopaminergic inhibition. This was studied by measuring the effect of domperidone, a selective dopamine D₂-receptor antagonist, on the carotid chemoreceptor response to O₂ and CO₂ in anesthetized neonatal and adult cats. The animals were exposed to four levels of isocapnic O₂ (arterial PO₂ of ~35-45, 55- 65, 80-90, >300 Torr) and four levels of isoxic CO₂ (end-tidal PCO₂ of ~21, 40, 58, and 78 Torr) before and after D₂-receptor blockade. Whole nerve activity was recorded from the carotid sinus nerve (CSN). Both neonatal and adult cats increase CSN activity during hypoxia and hypercapnia (P < 0.001). Domperidone caused an increase in CSN activity at all O₂ levels in adults (P < 0.01) but only during hypoxia in neonates (P < 0.001). Domperidone caused an increase in CSN activity during normo- and hypercapnia in adults but only during hypercapnia in neonates (P < 0.001). Domperidone approximately doubled an index of hypoxic sensitivity in the normoxia- hypoxia range (100 to 40 Torr) in the neonatal group but had little effect on sensitivity to hypoxia in adults. We conclude that the inhibitory role of endogenous dopamine in the carotid chemoreceptors changes with postnatal development.