Chronic intermittent hypoxia augments sympatho-excitatory response to ATP but not to l-glutamate in the RVLM of rats

The development of sympathetic overactivity and hypertension in rats submitted to chronic intermittent hypoxia (CIH) involve alterations in the central mechanisms controlling respiratory and autonomic functions. Herein, we assessed whether CIH alters glutamatergic and/or purinergic signaling in the ventrolateral medulla (VLM), a region that encompasses the pre-sympathetic neurons and respiratory neurons of the ventral respiratory column. Groups of juvenile rats were exposed for 10 days to CIH (6% O2 for 40 s, every 9 min, 8 h/day) or normoxia (controls). Following treatment, in situ working heart-brainstem preparations were performed to record simultaneously respiratory and sympathetic motor outputs. In separate CIH and control groups, the VLM was dissected for western-blot analyses of ionotropic glutamatergic and P2 receptors. l-glutamate microinjections (1, 3 or 10 mM) into VLM of control (n = 6) and CIH groups (n = 10) produced similar increases of sympathetic and abdominal activities associated with phrenic nerve inhibition; immunoreactive NMDAR1 and GluR2/3 densities at the VLM were also alike between groups (n = 4). In contrast, VLM microinjections of ATP (1, 10 or 50 mM) evoked larger sympatho-excitatory responses in CIH (n = 8) than in control rats (n = 7, P < 0.05) whilst the abdominal increase and phrenic nerve inhibition were of comparable magnitudes. The immunoreactive densities of P2X3 and P2X4 receptors, but not P2X1 and P2Y2, were 20% higher in VLM of CIH (n = 8; P < 0.05) than controls (n = 8). Altogether, our findings suggest that CIH augments purinergic signaling in the VLM, supporting the concept that nucleotides play a role in the dynamic central control of the sympathetic autonomic function.