Rabbit Ventilatory Responses to Peripheral Chemoexcitators: Effects of Chronic Hypoxia

Exposure to prolonged hypobaric hypoxia increases baseline ventilation and the ventilatory response to acute hypoxia, a phenomenon known as hypoxic ventilatory acclimatization (HVA). It is currently accepted that the carotid bodies and the reduced PO2 levels are key elements in the generation of the HVA. However, because most of these experiments have been performed in hypobaric conditions, we studied the effects of 15 days of chronic normobaric hypoxia (CNH) on the rabbit ventilatory responses to hypoxia and chemoexcitatory molecules. New Zealand White rabbits were placed in a 0.3 m(3) chamber with controlled temperature and a mean O-2 content of 9.17 +/- 0.09 %. Animals with or without CNH exposition (naive) were anesthetized (ketamine/xylazine 75/7.5 mg/kg, i.m.), cannulated and air flow was measured. In naive animals hypoxic challenges and NaCN increase ventilation, effect completely abolished after bilateral chemodenervation. However, ventilatory responses to nicotine, ATP and dopamine remained largely unchanged after bilateral chemodenervation, suggesting a centrally mediated effect for these drugs. Basal ventilation was reduced in CNH animals, but the dose dependent ventilatory increases induced by NaCN presented an increased sensibility. Further experiments are needed to elucidate the mechanisms responsible for these acclimatized responses.