Ventilatory stimulation by dopamine‐receptor antagonists in the mouse

Abstract

1 Ventilation was measured by a plethysmographic method in awake mice before and after intraperitoneal injection of neuroleptic drugs to test the hypothesis that dopaminergic mechanisms modulate control of breathing in this species. 2 Dose-dependent augmentation of ventilation at rest and during hypoxia, and reduced ventilation during hypercapnia was demonstrated for haloperidol, droperidol, prochlorperazine and chlorpromazine (P < 0.05 or less for each drug). 3 Doses of drugs causing maximal increase of the ventilatory response to hypoxia were linearly related (r = 0.98, P <0.001) to in vitro affinity of the drugs for dopamine receptors. 4 Despite presumed equal dopamine-receptor blockade, the drugs had unequal effects on the ventilatory response to hypoxia. Droperidol augmented hypoxic ventilation to 290% of the control value, chlorpromazine to 250% control, prochlorperazine to 190% control and haloperidol to 120% control. These differences in efficacy were in the same order as the affinities of the drugs for aadrenoceptors. 5 The effect of combined haloperidol (90 nmol kg-') and varying doses of phentolamine (175-900 nmol kg-') was assessed to test the hypothesis that ax-antagonism was a factor in determining the increase in ventilation following dopamine blockade. Phentolamine caused dose-dependent augmentation of the ventilatory effects of haloperidol (P < 0.01) but had no ventilatory effect when given alone. 6 Carotid body resection in anaesthetized mice abolished the stimulation of hypoxic ventilation caused by droperidol. 7 It is concluded that dopaminergic mechanisms in the carotid body modulate ventilatory control in the awake mouse. The drugs most effective in augmenting hypoxic ventilation are those that block both dopamine and a-adrenoceptors.

Dobutamine potentiates arterial chemoreflex sensitivity in healthy normal humans

“…Inhibitory effects of dopamine are selectively mediated by dopaminergic receptors because they are seen only at low-dose dopamine infusion directed at dopaminergic receptor stimulation (3-5 g⅐kg Ϫ1 ⅐min Ϫ1 ), without stimulation of ␣or ␤-adrenoreceptors (36,37). These effects are not suppressed by ␣or ␤-adrenergic receptor blockade but are inhibited by haloperidol, a specific dopamine receptor antagonist (1,8,16,18,(26)(27)(28). Conversely, ␤-adrenoceptor agonism with larger doses of dopamine (10-12 g⅐kg Ϫ1 ⅐min Ϫ1 ) enhances the ventilatory response to hypoxia through sensitization of the peripheral chemoreceptors (37).…”

Carotid chemoreceptor denervation does not impair hypoxia-induced thermal downregulation but vitiates recovery from a hypothermic and hypometabolic state in mice

“…Several methods to eliminate CB function in animals have been published. Surgical methods comprise complete resection 49 , 50 or glossopharyngeal nerve denervation 27 , 31 , 51 , whereas selective interference with CB function has been performed pharmacologically 52 and genetically 53 , 54 . In this study, bilateral surgical denervation was performed to ensure complete loss of CB function.…”

Effects of low‐dose dopamine on ventilation in patients with chronic obstructive pulmonary disease

“…It is abundant in type I cells (glomus cells) in the carotid sinus of animals and humans [7–12] and low‐dose dopamine infusion is associated with decreased carotid sinus drive and diminished ventilatory response to hypoxia in many animal species [13–16]. Dopaminergic receptor antagonists prevent the depressant effect of dopamine on ventilation and enhance the ventilatory response to hypoxia [17–19]. Low‐dose dopamine blunts the ventilatory response to isocapnic hypoxia in healthy subjects [20,21], an effect which is abolished by the dopaminergic receptor blocker, haloperidol [22].…”