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 approximately 35-45, 55-65, 80-90, > 300 Torr) and four levels of isoxic CO2 (end-tidal PCO2 of approximately 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.
Tomares
S M
SM
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore 21287.
Bamford
O S
OS
Sterni
L M
LM
Fitzgerald
R S
RS
Carroll
J L
JL
D000818:Animals; D002245:Carbon Dioxide / Q000633:toxicity; D002344:Carotid Body / Q000187:drug effects* / Q000254:growth & development; D002346:Carotid Sinus / Q000294:innervation / Q000502:physiology; D002415:Cats; D004294:Domperidone / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000633:toxicity; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D015656:Respiratory Mechanics
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D002245:Carbon Dioxide; D004294:Domperidone; D010100:Oxygen