Dopamine blockade alters ventilatory acclimatization to hypoxia in goats

Dopamine (DA) is generally accepted to be an inhibitory neurotransmitter in the carotid body (CB). It is released and depleted from the CB by acute hypoxia. From this background we made the hypothesis that hypoxic depletion of CB DA could be responsible for a time-dependent increase in CB afferent output and the early phase of ventilatory acclimatization to hypoxia (VAH) in goats. We reasoned, then, that blockade of DA receptors in the CB would accelerate the time course of VAH in the goat, i.e. produce a greater acute response to hypoxia (first 15 min) followed by a reduced rate of change of the subsequent time-dependent hyperventilation. We tested this hypothesis by exposing 7 adult female goats to up to 28 h of hypobaric hypoxia (PB = 380 Torr) on 3 different occasions separated by at least 2 months. The first was as control. During the second and third exposures different doses of the DA antagonist, domperidone, were administered prior to and during the hypoxic exposure (0.5 mg/kg followed by 0.25 mg/kg every 3 h and in the second study 1.0 mg/kg followed by 0.5 mg/kg every 2 h). The time course of acclimatization was assessed by measurement of arterial blood gases and pH in the awake goats. The data obtained in the first 4-5 h of hypoxia in domperidone treated animals appeared to support the hypothesis. Domperidone treated animals had a significantly greater acute ventilatory response to hypoxia followed by a lower rate of progressive hyperventilation in this period. However, variation in control values, greater respiratory alkalosis and a secondary significant hyperventilation after 6-7 h of hypoxia in the domperidone treated animals prevents a clear conclusion as to the precise role of CB dopaminergic mechanisms in acclimatization to hypoxia. Nevertheless, peripheral DA receptor blockade with domperidone does alter the time course and magnitude of hyperventilation during the first 7 h of hypobaric hypoxia in goats.