Modulation of hypoxic ventilatory response by systemic platelet-activating factor receptor antagonist in the rat

Platelet activating factor (PAF) has recently emerged as an important modulator of neuronal excitability by enhancing synaptic glutamate release. Since PAF receptors (PAFR) are ubiquitously distributed in the brain, we hypothesized that PAF may play a role in respiratory control. To examine this issue, hypoxic (10% O 2 for 15 min, n=14) and hypercapnic (5% CO 2 for 30 min, n=6) challenges were performed in chronically-instrumented, unrestrained adult rats following administration of the pre-synaptic PAFR antagonist BN52021 (i.p. 20 mg/kg in 0.5 ml) or vehicle (Veh). In normoxia, BN52021 elicited Vt decreases and corresponding f increases such that minute ventilation ( V ̇ e) was unaffected. During hypercapnia, peak V ̇ e increased similarly after both treatments (103±18% in BN52021 vs. 94±19% in Veh, p-NS). In contrast, significant reductions in the peak hypoxic V e response occurred after BN52021 (42±10% vs. 104±18% in Veh, P