Dopaminergic control of respiration as shown by effects of 4-aminopyridine

The dopaminergic control of respiration in conscious and urethane-anaesthetized rabbits, was studied by comparing the respiratory effects of 4-aminopyridine alone (4-AP; 1 mg/kg i.v.) and those after the administration of dopamine antagonists (domperidone and haloperidol; 1 mg/kg each). The respiratory rate in conscious rabbits was increased by 4-AP. After domperidone this increase was reduced and preceded by a transient decrease. In spontaneously breathing, anesthetized rabbits there was a transient reduction after which the respiratory rate was increased by 4-AP; tidal volume was affected in an inverse manner. After domperidone, the excitatory effect of 4-AP on respiratory rate and the inhibitory effect on tidal volume were blocked. The effects of 4-AP on respiratory rate were prevented by vagotomy. In anesthetized, vagotomized, paralyzed and artificially ventilated rabbits (VPV animals) the peak amplitude of the integrated phrenic nerve activity ("phrenic activity') was increased by 4-AP. After pretreatment with haloperidol this effect of 4-AP on phrenic activity was reduced while the respiratory rate was now increased. In VPV animals with denervated carotid bodies the excitatory effect of 4-AP on phrenic activity was strongly enhanced and respiratory rate was increased. These effects were slightly reduced but not blocked by haloperidol. It is concluded that endogenous dopamine is involved in the control of respiration through effects on peripheral mechanisms (inhibition of inspiratory activity and enhancement of respiratory rate) as well as on central mechanisms (stimulation of inspiratory activity and reduction of respiratory rate).