Dopaminergic modulation of respiratory timing mechanisms in carotid body-denervated dogs

The role of central dopaminergic mechanisms in ventilatory control was investigated by monitoring phrenic motorneuronal output of anesthetized dogs which were vagotomized, paralyzed and artificially ventilated and in which bilateral carotid body denervation had been performed. Intravenous administration of dopamine (DA) had no effect on phrenic output in these dogs. In contrast, apomorphine (APO), a potent dopaminergic agonist, which unlike dopamine, crosses the blood-brain barrier consistently and significantly prolonged inspiratory duration and shortened expiratory duration without altering phrenic amplitude. The dopaminergic antagonist haloperidol produced a frequency-dependent decrease in basal phrenic minute activity and reversed or abolished APO-induced changes in the phrenic profile. These data verify the specificity of APO for dopamine receptors and further suggest that DA receptors in the central nervous system exert a tonic effect on central respiratory control mechanisms. In contrast, domperidone, a dopaminergic antagonist which poorly penetrates the blood-brain barrier did not alter basal phrenic characteristics. Moreover, with the exception of inspiratory duration, domperidone did not antagonize APO-induced alterations in the phrenic profile. We conclude that dopaminergic mechanisms within the brain or spinal cord modulate timing relationships of central respiratory output.