Purinergic modulation of hypoxic regulation via the rostral ventral lateral medulla in rats

Anatomical studies have demonstrated the existence of purinergic receptors in the rostral ventral lateral medulla (RVLM), a site containing some respiratory-related neurons. However, little is known about the functional role of these receptors in acute hypoxia. In the present study, we found that both the amplitude and frequency of phrenic nerve discharges were increased during hypoxia. Microinjection of adenosine 5'-triphosphate (ATP) (0.2M, 10-70nl) into the RVLM increased the hypoxic respiratory response and showed significant dose-dependency. An identical microinjection protocol of pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS), a broad-spectrum P2 receptor antagonist, into the RVLM markedly attenuated the respiratory effects evoked by hypoxic ventilation. Immunohistochemical analysis showed that the P2X(2) receptor was present in the postsynaptic membrane of the RVLM neuronal cell bodies and levels of this receptor were significantly increased after acute hypoxic challenge. These results suggest that RVLM purinergic P2 receptors may contribute to respiratory control by regulating the acute hypoxic ventilatory response.