We tested the hypothesis that the function of cholinergic-nicotinic receptors on respiration
is age dependent. To this end, we used whole body plethysmography to measure breathing
frequency (fR), tidal volume (V(T)) and minute ventilation (V (E)) under normoxia
(21% O(2)) in rats at 1, 4, 7, 12 and 21 postnatal days before and after administration
of epibatidine (nicotinic agonist 5 microg/kg, i.p.). In normoxia, epibatidine increased
fR and V (E) in a proportionally age-dependent manner (p for age <0.001), without
affecting V(T). We then focused on P4 and P12 rats, as representative of this developmental
pattern, to measure ventilatory response to moderate hypoxia (12% O(2), 20 min) after
i.p. injection of saline (control), epibatidine (5 microg/kg), or (nicotinic antagonist,
1mg/kg). At these doses, both drugs selectively target peripheral nicotinic receptors.
Epibatidine enhanced the hypoxic ventilatory response while hexamethonium significantly
reduced it. These effects were significantly greater in P12 than in P4 rats (p for
age <0.001). In P12 rats, in vitro recordings of carotid sinus nerve activity showed
that superfusion with nicotine enhanced chemosensory discharge rate in normoxia and
hexamethonium reduced the discharge rate in hypoxia. We also identified the nicotinic
receptor alpha7 subunit by immunohistochemistry in carotid bodies from P12 rat. These
data show that the role of cholinergic-nicotinic receptor on hypoxic chemoreflex is
age dependent and this effect likely implicates carotid body nicotinic receptor activation.