Domperidone-induced potentiation of ventilatory responses in awake goats

Dopamine has been implicated in maintaining tonic inhibition of carotid body activity. We tested this hypothesis by assessing the ventilatory effects of a peripheral dopamine antagonist, domperidone. The effects of this agent on the ventilatory responses to hypoxia and hypercapnia were also examined. The study was performed in awake carotid body intact and carotid body denervated goats. Resting minute ventilation increased while PaCO2 decreased (4 Torr) following domperidone administration (0.5 mg/kg, I.V.) in carotid body intact goats. This response did not occur in carotid body denervated goats supporting the hypothesis that endogenous dopamine provides tonic inhibition in the carotid body. Hypoxic and hypercapnic ventilatory responses were significantly augmented following domperidone administration in the carotid body intact goats. This supports the concept of dopaminergic modulation of the response of the carotid body to stimuli. Domperidone allows study of carotid chemoreceptor dopaminergic activity in awake animals because of its high affinity for carotid body D2 dopamine receptors and its lack of CNS effects.