The effect of intracerebroventricular dopamine administration on the respiratory response to hypoxia

Acute hypoxia produces an increase in ventilation. When the hypoxia is sustained, the initial increase in ventilation is followed a decrease in ventilation. The precise mechanism of this decline in ventilation during sustained hypoxia is unknown. Recent studies hypothesized that the accumulation of dopamine in the central nervous system might have a major role in production of hypoxic respiratory depression. The purpose of this study was to examine whether dopamine has an effect on occurance of central ventilatory depression which is seen in acute hypoxia in peripheral chemoreceptors denervated animals. The experiment were conducted in rabbits anesthetized with Na-pentobarbital (25 mg x kg(-1) i.v.). For intracerebroventricular (i.c.v.) injections of dopamine (1 microg) in each animal, canula was placed in left lateral cerebral ventricle by stereotaxic method. Respiratory frequency (f x min(-1)), tidal volume (V(T)) ventilation minute volume (V(E)) and systemic arterial blood pressure (BP) were recorded during air and 3 minutes hypoxic gas mixture (8%O2-92%N2) breathing. I.c.v. administration of dopamine during normoxia decreased V(T), f, V(E) and BP, significantly. When rabbits were injected with an i.c.v. dopamine on hypoxic gas mixture breathing in control animals, there was depression of hypoxic ventilatory responses. After i.c.v. administration of dopamine antagonists haloperidol (0.1 mg) and domperidone (0.07 mg) in chemodenervated rabbits, the significant increases in V(T), V(E) and BP were observed. On the breathing of hypoxic gas mixture of chemodenervated and i.c.v. dopamine antagonists administrated rabbits, hypoxic depression was completely abolished. These results of this study show that accumulation of dopamine in the brain seems to reduce the response of the central control mechanisms to chemoreceptor impulses during normoxia and hypoxia. In conclusion present study suggests important role played by central dopaminergic pathways in the occurence of acute hypoxic ventilatory depression.