Abstract
Dopamine levels in rat carotid bodies and the effects of intravenous dopamine injections on respiration in adult rats anaesthetized with pentobarbitone have been studied in animals which were treated with capsaicin neonatally. Levels of dopamine were five fold higher in the carotid bodies of capsaicin-treated rats as compared with vehicle-treated controls, but there was no significant difference between capsaicin-treated and vehicle-treated rats in their ID50 values for dopamine-induced respiratory depression. Domperidone, a dopamine D2-receptor antagonist, substantially reduced the respiratory depression caused by dopamine, both in capsaicin-treated and in control animals, suggesting that a D2-receptor was involved in the response. Cutting the carotid sinus nerves greatly reduced the ventilatory-depressant effect of dopamine, showing that sensory receptors, most probably arterial chemoreceptors, were responsible for most of the response. Substantially less reflex hyperventilation was evoked in capsaicin-treated rats by the peripheral chemoreceptor stimulants hypoxia and sodium cyanide, in comparison with the controls, and domperidone did not increase the responsiveness. About 80% of the reflex ventilatory change originated from carotid body chemoreceptors. The hypoventilation caused by breathing 100% O2 was not significantly different in capsaicin-treated rats when compared with controls. Domperidone substantially reduced this response in capsaicin-treated rats, but not in vehicle-treated animals. Dopamine-induced respiratory depression in capsaicin-treated rats was slightly enhanced, rather than reduced, by oxygen breathing; domperidone remained an effective antagonist of dopamine-induced ventilatory depression. Most of the reduction in respiration caused by dopamine in rats anaesthetized with pentobarbitone can be attributed to actions on a dopamine D2-receptor located in the carotid body. However, despite the increased levels of dopamine found in the carotid bodies, the reduced peripheral chemosensitivity observed in anaesthetized capsaicin-treated rats does not appear to result from a change in sensitivity to dopamine.